| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
and CD8ß Induce Nitric Oxide Production and Associated Killing of the Parasite Leishmania major1
Departments of
*
Medicine and
Biological Sciences, University of Alberta, Edmonton, Alberta, Canada
Prior studies demonstrated that rat macrophages express CD8, which
differs from T lymphocyte CD8 within the ligand binding domain. We
investigated whether stimulation of macrophage CD8 could induce
mediator release and regulate host defense. Cross-linking either CD8
(OX8, 5 µg/ml) or CD8ß (341, 10 µg/ml) stimulated nitric oxide
(NO) production, which correlated with an up-regulation of inducible NO
synthase protein. Cell signaling inhibitors were used to elucidate the
pathways of CD8 and CD8ß stimulation. Genistein (broad spectrum
protein tyrosine kinase inhibitor, 10 µg/ml), PP1
(src family kinase inhibitor, 5 µg/ml), polymyxin
B (protein kinase C (PKC) inhibitor, 100 µg/ml), and Ro 31-8220 (PKC
inhibitor, 1 µM) significantly inhibited anti-CD8- and
anti-CD8ß-stimulated NO production and inducible NO synthase
up-regulation, suggesting that tyrosine kinase(s)
(src family) and PKC are involved in CD8 signaling.
In addition, cross-linking CD8 stimulated NO-dependent macrophage
killing of the parasite Leishmania major. For the first
time, this work demonstrates that the ß-chain of macrophage CD8, in
addition to the -chain, can regulate mediator release. These results
further illustrate the importance of this molecule and support our
previous data demonstrating differences between macrophage and T
lymphocyte CD8. Additional studies on the signaling mechanisms and
possible ligand(s) for macrophage CD8 will lead to a greater
understanding of inflammation and host defense.
This article has been cited by other articles:
|
|
 |
|
  D. Gibbings and A. D. Befus CD4 and CD8: an inside-out coreceptor model for innate immune cells J. Leukoc. Biol., August 1, 2009; 86(2): 251 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mookerjee Basu, A. Mookerjee, P. Sen, S. Bhaumik, P. Sen, S. Banerjee, K. Naskar, S. K. Choudhuri, B. Saha, S. Raha, et al. Sodium Antimony Gluconate Induces Generation of Reactive Oxygen Species and Nitric Oxide via Phosphoinositide 3-Kinase and Mitogen-Activated Protein Kinase Activation in Leishmania donovani-Infected Macrophages. Antimicrob. Agents Chemother., May 1, 2006; 50(5): 1788 - 1797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schroeter, G. Stoll, R. Weissert, H.-P. Hartung, H. Lassmann, and S. Jander CD8+ Phagocyte Recruitment in Rat Experimental Autoimmune Encephalomyelitis: Association with Inflammatory Tissue Destruction Am. J. Pathol., October 1, 2003; 163(4): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Campos-Neto, J. R. Webb, K. Greeson, R. N. Coler, Y. A. W. Skeiky, and S. G. Reed Vaccination with Plasmid DNA Encoding TSA/LmSTI1 Leishmanial Fusion Proteins Confers Protection against Leishmania major Infection in Susceptible BALB/c Mice Infect. Immun., June 1, 2002; 70(6): 2828 - 2836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Nohara, M. Kulka, R. E. Dery, F. L. Wills, N. S. Hirji, M. Gilchrist, and A. D. Befus Regulation of CD8 Expression in Mast Cells by Exogenous or Endogenous Nitric Oxide J. Immunol., November 15, 2001; 167(10): 5935 - 5939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-J. Lin, N. Hirji, G. R. Stenton, M. Gilchrist, B. J. Grill, A. D. Schreiber, and A. D. Befus Activation of Macrophage CD8: Pharmacological Studies of TNF and IL-1{beta} Production J. Immunol., February 15, 2000; 164(4): 1783 - 1792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. R. Allen, J. McHale, J. Smith, H. T. Cook, A. Karkar, D. O. Haskard, R. R. Lobb, and C. D. Pusey Endothelial Expression of VCAM-1 in Experimental Crescentic Nephritis and Effect of Antibodies to Very Late Antigen-4 or VCAM-1 on Glomerular Injury J. Immunol., May 1, 1999; 162(9): 5519 - 5527. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
