Indian Journal of
Biochemistry & Biophysics
CODEN : IJBBBQ ISSN : 0301-1208
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VOLUME 44 |
NUMBER 5 |
OCTOBER 2007 |
Special Issue
Molecular and Clinical Immunology in Health and Disease
FOREWORD
It is indeed a pleasure to know that the Indian Journal of Biochemistry and Biophysics (IJBB), a peer-reviewed journal published by National Institute of Science Publication and Information Resources (NISCAIR), New Delhi, a constituent establishment of Council of Scientific and Industrial Research (CSIR) is publishing some of the invited talks/papers of 33rd Indian Immunology Society (IIS) conference held at A.I.I.M.S., New Delhi during 28-31 January 2007. The very intent of the Editor, IJBB, Director, NISCAIR and IIS, particularly the organizing secretary, Prof. D N Rao (Department of Biochemistry, A.I.I.M.S.) in disseminating such information, precisely on the issues related to public health is commendable.
The focus of the special number is the theme of the conference, “Molecular and Clinical Immunology in Health and Disease” is quite topical and often enjoys considerable attention from all quarters including students, researchers, clinicians, industry and the Government. The articles presented in this issue are contributed by the eminent scientists working in the areas of basic and applied immunology. It is for the first time that the ‘Indian Journal of Biochemistry and Biophysics’ is bringing out a dedicated issue on such a theme with the guidance and support of ‘Indian Immunology Society’ with full length articles, in the form of Minireviews and original research papers, presented in the conference either as full papers, talks, or as posters. It is pertinent to mention that not only papers from established groups in the area of research are included but also promising emerging groups have been encouraged through their significant contributions.
Minireviews on HIV-1, Tuberculosis pathogen, Typhoid, Prodigiosins, NO immune response, iNOS in asthma pathogenesis, COX-2 on lung tumor progression, role of T-cells in diabetic pregnancy, Viral complement regulators and Phosphatidylinositol kinases in cell signaling contributed by experts in the respective field of research are no doubt a valuable treasure for readers. Research articles on role of IL-10 in cervical cancer, ALL diagnosis and clinical remission, Liposomal delivery of M. leprae antigens, Immunomodulatory role of lipoarabinomannan, Activation of polymorphonuclear nutrophils in diabetes and oxidative stress, Acetylcholinesterase isozymes from Setaria cervi, Circulatory Ig levels and MOR alleles, and UDS pathogenesis are equally interesting and with their contents would prove to be a reservoir of research data with immense citation potential.
The efforts taken by the editorial team in publishing this excellent number and the professional touch provided by Prof. Rao, the organizing secretary of the conference are explicit in the flawless outcome. I see this association between IJBB and IIS as just a beginning for public good, and wish this societal relationship continue to flourish. I wish more such publications, special numbers for ‘Indian Journal of Biochemistry and Biophysics’ to benefit the readers.
(Prof. N K GANGULY)
Director General,
Indian Council of Medical Research (ICMR)
New Delhi
CONTENTS
Minireviews
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Human Immunodeficiency Virus-1 Tat Protein: Immunological Facets of |
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Cellular AATF Gene: Armour against HIV-1 |
276 |
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Mycobacterium tuberculosis and Dendritic Cells:
Recognition, Activation and |
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Aprajita Sinha, Nasir
Salam, Shashank Gupta and Krishnamurthy Natarajan* |
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Type II Phosphatidylinositol 4-kinase(s) in Cell
Signaling Cascades |
289 |
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Prodigiosins: A Novel Family of Immunosuppressants
with Anti-cancer Activity |
295 |
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Inducible Nitric Oxide Synthase (iNOS): Role in Asthma Pathogenesis |
303 |
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Nitric
Oxide and Immune Response
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310 |
Parul Tripathi
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Immunological, Cellular and Molecular Events in
Typhoid fever |
320 |
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Viral Complement Regulators: The Expert Mimicking
Swindlers |
331 |
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Muzammil
Ahmad, Kalyani Pyaram, Jayati Mullick and Arvind Sahu* |
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Role of T-cells in
Diabetic Pregnancy and Macrosomia |
344 |
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Papers |
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Role of IL- |
350 |
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Comparative analysis of differential expression of sialic acids and
adhesion molecules |
357 |
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Suchandra Chowdhury, Suman Bandyopadhyay, Sarmila Chandra
and Chitra Mandal* |
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Immunomodulatory role of arabinosylated lipoarabinomannan on Leishmania donovani infected murine
macrophages |
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Surajit Bhattacharjee, N
Majumder, P Bhattacharyya, |
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Advanced glycosylated end products-mediated activation of
polymorphonuclear neutrophils in diabetes mellitus and associated oxidative
stress |
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Anjali Gupta, A K
Tripathi*, R L Tripathi, S V Madhu and B D Banerjee |
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Partial purification and
characterization of acetylcholinesterase isozymes from adult bovine filarial
parasite Setaria cervi |
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Shravan K Singh, Deep C
Kaushal, P Kalpana Murthy and Nuzhat A Kaushal* |
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Liposomal delivery of Mycobacterium
leprae antigen(s) with murabutide and Trat peptide inhibits Fas-mediated
apoptosis of peripheral blood mononuclear cells derived from leprosy patients |
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Correlation of circulatory immunoglobulin levels
with Mu opiate receptor allele |
394 |
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Shashwat Sharad, A K
Gupta, R A Singh, Manav Kapoor and Suman Kapur* |
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Role of virulence plasmid of Aeromonas
hydrophila in the pathogenesis of ulcerative disease syndrome in Clarias batrachus |
401 |
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Tanmay Majumdar, S
Datta, D Ghosh, S Dutta, A Chakraborty, R Goswami and |
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407 |
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412 |
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*Author
for correspondence
Call
for Nominations
Dr H.P. Heineken Prizes for Biochemistry and Biophysics and
Medicine 2008
Nominations
are being accepted for the prestigious Dr H. P. Heineken Prizes (award
worth USD 1,50,000) for Biochemistry and Biophysics and
Medicine 2008. Presented since 1964, the award in the field
of biochemistry and biophysics is intended to encourage outstanding scientific
achievements in the fields of biochemistry and biophysics, including the
biochemical and biophysical aspects of microbiology, and the physiology of seed
germination. Awarded since 1989, the prize in medicine is intended to encourage
outstanding scientific achievements in the fields in medicine. The Royal
Netherlands Academy of Arts and Sciences (KNAW) selects the winners of the Heineken prizes from around the world.
Candidates may be nominated by either an organization or an
individual researcher. The deadline for nominations is 1 January 2008.
For more information and nomination forms, please
visit http://www.knaw.nl/heinekenprizes/
MINIREVIEWS
Indian Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.269-275
Human Immunodeficiency
Virus-1 Tat Protein: Immunological Facets of a Transcriptional Activator
Shalini Gupta and Debashis Mitra*
National Centre
for Cell Science,
Received 22 May 2007; revised 20 September 2007
Human immunodeficiency virus-1 (HIV-1) infection is characterized by chronic immune activation and progressive loss of CD4+ T cells, leading to a wide array of immune dysfunction, particularly involving immune response directed against viral antigens. HIV-1 encodes for fifteen proteins, which might serve as a target for immune recognition. Immune response to the envelope proteins have been studied more due to their presence on the surface of the virus. Recent studies on HIV vaccine development have focused on the Gag and Pol proteins. The transactivator Tat and Rev proteins have also been the focus of immunization studies due to their potent regulatory activity. The Tat (transactivator of transcription) protein although being nuclear in localization is also released from infected cells and acts on uninfected cells. Extracellular Tat seems to play an important role in AIDS pathogenesis. Furthermore, a correlation has been found between anti-Tat immune response and slow progression of the disease. Although several studies have shown Tat as a potential vaccine candidate with encouraging results, there are also reports raising doubt about its efficacy in multi-component HIV vaccine strategy. Here, we have addressed the issue of immune response to the most indispensable HIV-1 regulatory protein Tat.
Keywords: HIV-1, Tat, Vaccine, Cytokine,
Transcription Activator, Immunosuppression
E-mail: dmitra@nccs.res.in
Minireview
Indian Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.276-278
Cellular AATF Gene: Armour
against HIV-1
Deepak Kaul*
Molecular Biology Unit,Department of
Experimental Medicine & Biotechnology,
Postgraduate Institute of Medical Education & Research,
Received 30 April 2007; revised 07 September 2007
Outcome of HIV-1 infection at the cellular level is decided by the orchestrated balance that exists between cellular nucleic acid-based adaptive immune mechanism involving non-coding micro RNAs (miRNAs) and offensive tactics of HIV-1 to suppress this host cellular immunity. In this context, the review explains the importance of a novel miRNA encoded exclusively and conspicuously by HIV-1 genome that has the ability to specifically target cellular AATF gene recognized to play a crucial role in the maintenance of adaptive immunity at nucleic acid level against HIV-1 invasion.
Keywords: HIV-1 RNomics, Cellular
AATF gene, CD4 Lymphopenia
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.279-288
Mycobacterium tuberculosis and Dendritic Cells: Recognition, Activation and Functional
Implications
Aprajita Sinha, Nasir Salam, Shashank Gupta and Krishnamurthy Natarajan*
Immunology Group, International Centre for Genetic Engineering and
Biotechnology, Aruna Asaf Ali Marg,
Received 26 June 2007; revised 05 September 2007
The highly complex nature of interactions of Mycobacterium tuberculosis with cells of the immune system has puzzled researchers the world-over in understanding the pathogenesis and immunology associated with tuberculosis (TB). This has contributed to the delay in development of effective vaccine(s) for TB. Several excellent studies have provided only a glimpse of the kind and degree of immune responses elicited following infection by mycobacteria. Preferred entry via respiratory route results in the capture of mycobacteria by alveolar macrophages that eventually become their long-term hosts. Since the pathogen is rarely cleared this has resulted in the human population serving as a large reservoir for mycobacteria. Owing to their unique ability to prime naïve and memory T cells, dendritic cells (DCs) play important and indispensable roles in the initiation and maintenance of protective immune responses following infection. The kind of immune response initiated by DCs with respect to mycobacteria determines the character of immune responses mounted by the host against the pathogen. The profile of cytokines and chemokines secreted as a result of infection of DCs by mycobacteria further plays an important role in defining the course of infection. This minireview attempts to highlight key interactions of mycobacteria with dendritic cells. We discus the uptake of mycobacteria by DCs followed by DC activation and the spectrum of immune responses initiated by infected/activated DCs, followed by numerous ways the pathogen has devised to subvert protective responses.
Keywords: Dendritic cells, Mycobacteria, Immune response,
Immune evasion, Mycobacterium
tuberculosis
Email: natarajan@icgeb.res.in
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.289-294
Type II Phosphatidylinositol
4-kinase(s) in Cell signaling Cascades
Ranjeet Kumar Sinha and Gosukonda Subrahmanyam*
Biotechnology Group,
Received 22 May 2007; revised 27 September 2007
Phosphorylated derivatives of phosphatidylinositol (PtdIns) are key components of many signaling cascades. Many isoforms of PtdIns kinases, PtdIns phosphate kinases and phosphatases use these lipids in amazing networks of signaling cascades that are yet to be understood fully. PtdIns 4-kinase(s) phosphorylates PtdIns at the 4th –OH position of inositol head group and are classified in to type II and III PtdIns 4-kinases. While type III PtdIns 4-kinases are implicated in vesicular trafficking, type II PtdIns 4-kinases are suggested to play a role in cell signaling, cytoskeletal rearrangements, cell motility and in microbial pathogenicity. This paper reviews the role of type II PtdIns 4-kinases in cell signaling cascades in health and disease.
Keywords: Lipid kinases; Cell signaling; Cytoskeleton; Cell adhesion; Microbial pathogenicity
E-mail: gsm@iitb.ac.in
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp. 295-302
Prodigiosins: A Novel Family
of Immunosuppressants with Anti-cancer Activity
Ruchi Pandeya*, Ramesh Chanderb and
aRadiation
Biology and Health Sciences Division, bFood Technology Division, cBio-Medical
Group, Modular Laboratories,
Bhabha Atomic Research Centre, Trombay, Mumbai 400 085, India
Received 22 May 2007; revised 16 August 2007
Prodigiosins (PrGs) are a family of promising therapeutic molecules, isolated mostly from Gram-negative bacteria and characterized by a common pyrryldipyrrylmethene structure with varying side chains. They show a broad spectrum of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive. PrGs are attracting increasing attention due to the ongoing research for less toxic, but effective agents for cancer chemotherapy and immunosuppression for preventing allograft rejection and autoimmunity. Different analogues have been synthesized and evaluated. This review discusses the immunosuppressive and anti-cancer activities of this class of compounds, as both involve inhibition of cell proliferation. The main focus is on the in vitro and in vivo immunosuppressive activity of the different PrGs and the mechanisms involved. PrGs primarily target the T cells, though some effects are observed on other cell types also. Unlike the well-known immunosuppressant cyclosporin A, PrGs do not inhibit the secretion of IL-2 but inhibit the mitogenic signaling from IL-2, suggesting a different mechanism of action. Janus tyrosine kinase 3 (Jak3) that associates with IL-2R upon activation is considered as the molecular target for PrGs. Its restricted expression makes Jak3 as an attractive target for immunosuppressive therapy. However, the available literature suggests that some other pathways are also influenced by the PrGs. These may be important for the anti-cancer activity, as well as immunosuppressive action. Therefore, PrGs appear to be potential candidates for pharmaceutical development as immunosuppressants and also as anti-cancer agents.
Keywords: Prodigiosins, Immunosuppressants, Anti-cancer activity
E-mail: ruchipandey01@gmail.com
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.303-309
Inducible
Nitric Oxide Synthase (iNOS): Role in Asthma Pathogenesis
Jyotsna Batra,
Rajshekhar Chatterjee and Balaram Ghosh*
Molecular Immunogenetics Laboratory,
Received 20 June 2007; revised 06 September 2007
Asthma is one of the most common chronic inflammatory
disorder of the airways of the lungs, affecting more than 300 million people
all over the world. Nitric oxide (NO) is endogenously produced in mammalian
airways by nitric oxide synthase (NOS) and is known to regulate many aspects of
human asthma, including the modulation of airway and vascular smooth muscle
tone and the inflammation. Asthmatic patients show an increased expression of
inducible nitric oxide synthase (iNOS) in airway epithelial cells and an
increased level of NO in exhaled air. Using
various NO inhibitors (non-specific or iNOS-specific) and gene knock-out
experiments, controversial results have been obtained regarding iNOS’s
beneficial and deleterious effects in the disease. In the present review, we
have attempted to summarize the results of these experiments and also the
genetic studies being undertaken to understand the role of iNOS in asthma. It
is argued that extensive biochemical, clinical and genetic studies will be
required to assess the precise role of NO in the asthma. This may help in
designing selective and more potent iNOS inhibitors and NO donors for
developing novel therapeutics for the asthma patients.
Keywords: iNOS, Asthma, Nitric Oxide, NOS inhibitor, Gene
E-mail: bghosh@igib.res.in
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.310-319
Nitric Oxide and Immune Response
Parul Tripathi*
Immunology Group,
International Centre for Genetic Engineering and Biotechnology,
Received 22
May 2007; revised 06 September 2007
Nitric oxide (NO), initially described as a physiological mediator of endothelial cell relaxation plays an important role in hypotension. It is an intercellular messenger and has been recognized as one of the most versatile players in the immune system. Cells of the innate immune system – macrophages, neutrophils and natural killer (NK) cells use pattern recognition receptors to recognize molecular patterns associated with pathogens. Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO. In addition to macrophages, a large number of other immune system cells produce and respond to NO. Thus, NO is important as a toxic defense molecule against infectious organisms. It also regulates the functional activity, growth and death of many immune and inflammatory cell types including macrophages, T lymphocytes, antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role of NO in non-specific and specific immunity in vivo and in immunologically mediated diseases and inflammation is poorly understood. This review discusses the role of NO in immune response and inflammation and its mechanisms of action in these processes.
Keywords: Nitric oxide, iNOS (inducible nitric oxide
synthase), Th1/Th2 Cytokines, Immune response, Macrophage, Endothelial cells
E-mail: parultripathi@rediffmail.com
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.320-330
Immunological, Cellular and
Molecular Events in Typhoid Fever
Nowsheen Hamid and S K Jain*
Department of
Biotechnology,
Received 02 June 2007; revised 20 September 2007
Salmonella, a facultative
intracellular Gram-negative bacterium infects a wide range of hosts causing
several gastrointestinal diseases and enteric fever in humans and certain
animal species. Typhoid caused by Salmonella
typhi remains a major health concern in
Keywords: Outer membrane proteins, Pathogenesis, Salmonella, Typhoid, Vaccine, Virulence
Email:
skjain@jamiahamdard.ac.in
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.331-343
Viral Complement Regulators: The Expert
Mimicking Swindlers
Muzammil
Ahmad, Kalyani Pyaram, Jayati Mullick and Arvind Sahu*
National
Centre for Cell Science,
Received 22
May 2007; revised 20 September 2007
The complement system is a principal bastion of
innate immunity designed to combat a myriad of existing as well as newly
emerging pathogens. Since viruses are obligatory intracellular parasites, they
are continuously exposed to host complement assault and, therefore, have
imbibed various strategies to subvert it. One of them is molecular mimicry of
the host complement regulators. Large DNA viruses such as pox and herpesviruses
encode proteins that are structurally and functionally similar to human regulators
of complement activation (RCA), a family of proteins that regulate complement.
In this review, we have presented the structural and functional aspects of
virally encoded RCA homologs (vRCA), in particular two highly studied vRCAs,
vaccinia virus complement control protein (VCP) and Kaposi’s sarcoma-associated
herpesvirus complement regulator (kaposica). Importance of these evasion
molecules in viral pathogenesis and their role beyond complement regulation are
also discussed.
Keywords: Viral
complement evasion, Viral molecular mimicry, RCA, Complement, immune evasion,
KSHV, HHV-8, Vaccinia virus, Variola virus, Smallpox, HVS, RRV, Kaposica, VCP,
HVS-CCPH
Email: arvindsahu@nccs.res.in
Minireview
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.344-349
Role of T-cells in Diabetic Pregnancy and
Macrosomia
Naim Akhtar
Khan
UPRES EA 4183 Lipides & Signalisation Cellulaire, Université de Bourgogne,
Faculté des Sciences de la vie, 6, Boulevard
Gabriel, 21000
Received 22 May 2007; revised 14 August 2007
A number of studies have recently addressed the
correlationship between diabetic pregnancy/macrosomia and differentiation of
T-cells into Th1 and Th2 subsets. Diabetic pregnancy has been found to be
associated with a decreased Th1 phenotype and IL-4 mRNA expression. In
macrosomic offspring, high expression of IL-2 and IFN-g mRNA, but not of Th2 cytokines is observed, indicating that the Th1
phenotype is upregulated during macrosomia. T-cells of gestational diabetic
rats and their macrosomic offspring seem to present a defect in signal
transduction. Indeed, the recruitment of free intracellular calcium
concentrations from intracellular pool in T-cells of these animals is altered.
The phenotype of regulatory T-cells (T-Reg) is upregulated in diabetic
pregnancy and their infants. T-cells in diabetic pregnancy and macrosomic obese
offspring are in vivo activated.
Adipokines and peroxisome proliferator-activated receptor-a (PPARa) also seem to modulate the pro-inflammatory
cytokines in these pathologies. Hence, activation of the immune system might be
considered as one of the regulatory pathways including metabolic abnormalities
in these two pathologies.
Keywords: T-cells, Inflammation, Peroxisome proliferator-activated receptors,
Diabetic pregnancy, Macrosomia
Email: naim.khan@u-bourgogne.fr
Original Papers
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.350-356
Role of IL-
1Immunology, Advanced Centre for Treatment, Research and Education in Cancer, (ACTREC), 2Gynecology and Urology, 3Preventive Oncology, 4Radiation Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai 400012, India
Received 29 May 2007; revised 29 August 2007
Cervical cancer
is the second most common cancer in the women worldwide and the most frequent
in developing countries, including
Keywords: Cervical
cancer, Human papilloma virus, IL-10, Regulatory T cells (Tregs), Immune suppression
Email: schiplunkar@actrec.gov.in
Indian
Journal of Biochemistry & Biophysics
Vol. 44
October 2007, pp.357-365
Comparative analysis of differential expression of sialic acids and adhesion molecules on mononuclear cells of bone marrow and peripheral blood in childhood acute lymphoblastic leukaemia at diagnosis and clinical remission
Suchandra
Chowdhury, Suman Bandyopadhyay, Sarmila Chandra1 and Chitra Mandal*
Infectious Disease and Immunology Division,
Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road,
Kolkata 700032, India
1Kothari
Medical Centre 8/3,
Received 06 July
2007; revised 31 August 2007
Childhood acute lymphoblastic leukaemia (ALL) is characterized by the neoplasm of immature haematopoietic precursor cells (HPCs). We report significant differences between the expression of sialoglycoproteins and adhesion molecules on mononuclear cells (MNCs) of bone marrow (BM) and peripheral blood (PB) from individual children at diagnosis of the disease. Lymphoblasts in PB predominantly expressed 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs), sialic acid, α2-3 linked sialic acid, L- and P-selectins and vascular cell adhesion molecule -1 (VCAM-1) on their surface compared to BM, as determined with selective lectins and monoclonal antibodies (mAbs) by flow cytometric analysis. CD34+CD38+ cells present either in diagnostic PB or BM always showed enhanced expression of both α2-3 and α2-6 linked sialic acids, Neu5,9Ac2-GPs, L- and P-selectins and VCAM-1, compared to CD34+CD38- population, as confirmed by higher mean fluorescence intensity (MFI). Expression of ICAM-1 was reverse. However, MFI of Neu5,9Ac2-GPs was always higher both in CD34+CD38+ and CD34+CD38- population in PB compared to BM. Diverse trend of these cell surface macromolecules was observed during clinical remission. This is the first comparative study between PB and BM, where significant differential distribution of sialylated macromolecules and adhesion molecules was observed. Hence, supervising these cell surface macromolecules at various stages of treatment might help in minimal residual disease detection, identifying mobilization factor(s) and in isolation of normal HPCs for autologous BM transplantation.
Keywords: 9-O-Acetylated sialoglycoproteins, Childhood acute lymphoblastic
leukaemia, Flow cytometry, Haematopoietic precursor cells, Immunoglobulin (Ig)
superfamily cell adhesion molecules, Sialic acids, Selectins
E-mail: cmandal@iicb.res.in,
chitra_mandal@yahoo.com
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October 2007, pp.366-372
Immunomodulatory
role of arabinosylated lipoarabinomannan on Leishmania
donovani infected murine macrophages
Surajit Bhattacharjee, N Majumder, P Bhattacharyya,
Department of Microbiology, Bose Institute,
P-1/12, C.I.T. Scheme VIIM, Kolkata-700 054,
Received 23 June 2007 ; revised 27 September 2007
Arabinosylated lipoarabinomannan (Ara-LAM), a surface glycolipid antigen isolated from avirulent Mycobacterium smegmatis is involved in modulation of host cell signaling. In this study, we investigated Ara-LAM-mediated modulation of impaired immune responses during visceral leishmaniasis caused by protozoan parasite Leishmania donovani. Ara-LAM treatment at dose of 3 μg/ml in L. donovani infected murine peritoneal macrophages as well as J774A.1 macrophage cell line exhibited a distinct up-regulation of pro-inflammatory cytokines like TNF-a and IL-12 both at the protein and transcriptional level. In addition, generation of nitric oxide and iNOS expression were also observed. The present study showed that Ara-LAM was significantly effective in elimination of L. donovani parasites from both peritoneal as well as J774A.1 macrophages. Thus, it could be utilized as an immunomodulatory agent in prevention of leishmanial pathogenesis.
Keywords: Lipoarabinomannan,
Leishmaniasis, Cytokine, Nitric Oxide
Email: subrata@bic.boseinst.ernet.in
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.373-378
Advanced glycosylated end
products-mediated activation of polymorphonuclear neutrophils in diabetes
mellitus and associated oxidative stress
Anjali Gupta, A K Tripathi*, R L Tripathi, S V Madhu† and B D Banerjee
Department of Biochemistry and †Medicine,
University College of Medical Sciences and G.T.B. Hospital (University of
Delhi),
Dilshad Garden, Delhi-110 095, India
Received 05 July 2007; revised 30 September 2007
Two important consequences of hyperglycemia in diabetes are development of oxidative stress and formation of advanced glycation end products (AGE) which are known to be associated with diabetic complications. Relationship between AGE formation and development of oxidative stress (OS) is yet to be established. In the present study, the involvement of AGE in PMN-mediated ROS generation and the associated OS were investigated in type 2 diabetic mellitus (DM) patients. We assessed OS parameters (serum MDA, FRAP and GSH), PMN oxidative functions (respiratory burst and superoxide production) and total serum AGE in 90 subjects divided equally in three groups — control group, Group I consisting of type 2 diabetic patients without microvascular complications and Group II consisting of type 2 diabetic patients with microvascular complications. PMNs isolated from both groups (I and II) exhibited higher level of respiratory burst (RB) and produced increased amount of superoxide anion as compared to the controls. The increase was more pronounced in diabetes with complications, as compared to those without. Serum malondialdehyde (MDA) level was elevated, whereas glutathione (GSH) and ferric reducing ability of plasma (FRAP) levels were significantly reduced in diabetes as compared to the controls, suggesting the presence of oxidative stress in DM. A positive correlation between PMN oxidative function and OS parameters suggested the involvement of PMN in the development of OS in DM. Serum AGE level was also elevated in diabetic groups as compared to the controls. Further, the positive correlation between serum AGE level and PMN oxidative function suggested the involvement of AGE in increased RB and generation of reactive oxygen species (ROS) by resting diabetic PMN. The results of the study indicate that AGE-PMN interaction possibly upregulates NADPH oxidase, leading to enhanced ROS generation and thus contributes to the pathogenesis in diabetes.
Keywords: Advanced glycosylation end products, Polymorphonuclear
neutrophil, Reactive oxygen species, Oxidative stress, Diabetes mellitus
E-mail: aktripathiucms@hotmail.com
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.379-385
Shravan K Singh1, Deep C Kaushal2, P Kalpana Murthy1 and Nuzhat A Kaushal1*
Divisions
of Parasitology1 and Microbiology2, Central Drug Research
Institute, Lucknow-226 001,
Received 13 June 2007; revised 11 September 2007
Filariasis is a major health problem, affecting millions of people in tropical and sub-tropical regions of the world. The isolation and characterization of parasite-specific enzyme targets is essential for developing effective control measures against filariasis. Acetylcholinesterase (AchE, E.C. 3.1.1.7), an important enzyme of neuromuscular transmission is found in a number of helminths including filarial parasites and may be playing a role in host-parasite interactions. Earlier, we demonstrated the presence of two isozymes of AchE, different from the host enzyme in the human (Brugia malayi) and bovine (Setaria cervi) filarial parasites. In the present study, two isozymes of AchE (pAchE1 and pAchE2) were isolated from S. cervi adults and characterized biochemically and immunochemically. The AchE was partially purified on Con-A Sepharose column and then subjected to preparative polyacrylamide gel electrophoresis (PAGE) for separation of the isozymes. The AchE activity was localized by the staining of gel and the isozymes were isolated from the PAGE strips by electroelution. Both isozymes preferentially utilized acetylcholine iodide as substrate and were strongly inhibited by the true AchE inhibitor (BW284c51), suggesting that they were true AchE. The polyclonal antibodies produced against the isozymes showed significant cross-reactivity with B. malayi AchE, but not against the host enzyme. These findings suggested that both the isozymes were biochemically (in terms of their substrate specificity and inhibitor sensitivity) and immunochemically similar, but different from the host enzyme.
Keywords: Setaria cervi, Brugia malayi, Acetylcholinesterase, Bovine filarial parasite, Human filarial parasite, Filarial acetylcholinesterase
E mail: nuzhatkaushal@hotmail.com;
nuzhatkaushal@yahoo.com
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.386-393
Liposomal delivery of Mycobacterium leprae antigen(s) with
murabutide and Trat peptide inhibits Fas-mediated apoptosis of peripheral blood
mononuclear cells derived from leprosy patients
Vineeta Chattree1, Neena Khanna2, Vandana
Bisht1 and D
1Department
of Biochemistry, 2Department of Dermatovenereology, All India
Institute of Medical Sciences,
Ansari Nagar, New Delhi-110029
Received 26 May 2007; revised 06 September 2007
Protective immunity against intracellular pathogen Mycobacterium leprae is dependent on the activation of T cells. Repeated stimulation of T cells by M. leprae antigens MLCwA (M. leprae total cell wall antigen) and ManLAM (mannose capped lipoarabinomannan) may lead to apoptosis in leprosy patients. In the present study, inhibition of the Fas-induced apoptosis of peripheral blood mononuclear cells of leprosy patients was investigated using above M. leprae antigen(s), in combination with immunomodulators murabutide (MB) and a Trat peptide in particulate form (liposome). Incubation of the cells with particulate mode of antigen presentation led to both decreased percentage of propidium iodide (PI) positive cells and T cells expressing Fas-FasL, as well as decreased caspase-8/-3 activities in the lepromatous patients, thereby inhibiting apoptosis, while converse was true with stimulation with soluble antigen. Concurrently, there was an upregulation of anti-apoptotic protein Bcl-XL in the lepromatous patients, thereby inhibiting apoptosis. Thus, the liposomal formulation of antigen promoted proliferation of anergized T cell by inhibiting apoptosis through decreased expression of death receptors and caspase activities and increased expression of anti-apoptotic protein Bcl-XL in these patients.
Keywords: Leprosy, Anergy, Apoptosis, Fas-FasL, Caspase activity, Bcl-xL protein, liposome, Immunomodulator
E mail: dnrao311@rediffmail.com
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.394-400
Correlation of circulatory
immunoglobulin levels with Mu opiate receptor allele
Shashwat Sharad1,
1Center
for Biotechnology, Biological Sciences Group, BITS, Pilani-333031,
2Allahabad
Agricultural Institute- Deemed University, Naini,
3Institute
of Human Behaviour and Allied Sciences,
Received 22 May 2007; revised 27 September 2007
Opiates are known to induce immunosuppression in their users (addicts). Evidences supporting their role in suppressing a variety of immunological end points in addicts have been reported by several investigators. In the present study, we investigated the changes in serum immunoglobulin (Ig) levels and their correlation with Mu opiate receptor (MOR) genotypes. Eighty-seven users and forty-five non-users were recruited for the study. Genomic DNA, isolated from the peripheral blood, was used for genotyping for C17T and A118G polymorphism using PCR-RFLP method. The frequency of A and G alleles in non-users was 89% and 11% respectively, whereas in addicts, it was 67% and 33% respectively. Case control analysis between groups revealed that 118G allele was associated with opioid dependence [Chi square (X2) = 13.56, odds ratio (OR) = 3.90, confidence interval95% (CI95%) = 1.80-8.67, p = 0.000231]. C17T polymorphism showed no association with opioid dependence [(X2) = 0.9, O R = 2.49, CI95% = 0.528-16.12, p = 0.343]. Mean Ig levels, both IgG (student’s t-test = 2.2738, p = 0.007) and IgA (student’s t-test = 2.848, p = 0.0051) differed between opiate users and non-users. IgG and IgA levels were also significantly different in individuals with different MOR genotypes. Immunosuppression was observed in AA genotype-bearing individuals, while no suppression was seen in AG and GG genotypes bearing individuals. In case of C17T polymorphism, both CC and CT genotypes bearing individuals showed immunosuppression, as judged by circulating Ig levels.
Keywords:
Opiate addiction, Mu opiate receptor, Allele type, IgG, IgA, Immunosuppression,
Genotyping
E mail: s_kapur@bits-pilani.ac.in
Indian
Journal of Biochemistry & Biophysics
Vol. 44 October
2007, pp.401-406
Role of virulence plasmid of Aeromonas hydrophila in the pathogenesis
of ulcerative disease syndrome in Clarias
batrachus
T Majumdar, S Datta, D Ghosh, S Dutta, A Chakraborty, R Goswami
and
Immunobiology Laboratory,
Received 22 May 2007; revised 10 September 2007
Pathogenic Aeromonas hydrophila (strain VB21), a
multiple-drug resistance strain contains a plasmid of about 21 kb. After curing
of plasmid, the isolates became sensitive to antimicrobials, to which they were
earlier resistant. The cured bacteria exhibited significant alterations in
their surface structure, growth profile and virulence properties, and failed to
cause ulcerative disease syndrome (UDS) when injected into the Indian catfish Clarias batrachus. Routine biochemical
studies revealed that the plasmid curing did not alter the biochemical
properties of the bacteria. After transformation of the plasmid into cured A. hydrophila the bacterium regained its
virulence properties and induced all the characteristic symptoms of UDS when
injected into fish. Thus, the plasmid plays a pivotal role in the phenotype,
growth and virulence of
A. hydrophila and pathogenesis of
aeromonad UDS.
Keywords:
Ulcerative disease syndrome, Aeromonas
hydrophila, Clarias batrachus, Catfish,
Plasmid, Transformation
E mail: shibnath1@yahoo.co.in