HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nohara, O. Articles by Befus, A. D. Search for Related Content PubMed PubMed Citation Articles by Nohara, O. Articles by Befus, A. D.

Regulation of CD8 Expression in Mast Cells by Exogenous or Endogenous Nitric Oxide¹

Osamu Nohara^2,*, Marianna Kulka^2,, René E. Déry, Fiona L. Wills, Nadir S. Hirji, Mark Gilchrist and A. Dean Befus^3,

^* Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan; and Glaxo-Heritage Asthma Research Laboratories, Pulmonary Research Group, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada

We recently reported a novel CD8 molecule on rat alveolar macrophages and peritoneal mast cells (PMC). However, little is known about the regulation of CD8 expression and function on these cells. We investigated the regulation of CD8 expression on PMC by NO, because NO can regulate inflammatory responses and also because anti-CD8 Ab stimulates inducible NO synthase and NO production by PMC and alveolar macrophages. Ligation of CD8 on PMC with Ab (OX8) induced CD8 mRNA expression after 3–6 h, and flow cytometry demonstrated that OX8 treatment increased CD8 protein expression compared with PMC treated with isotype control IgG1. To test whether NO mediates the up-regulation of CD8, we used the NO donor S-nitrosoglutathione (500 µM) and NO synthase inhibitors (N^G-monomethyl-L-arginine and N^G-nitro-L-arginine methyl ester; 100 µM). S-nitrosoglutathione up-regulated both mRNA and protein expression of CD8 in PMC compared with that in sham-treated cells, while NO synthase inhibitors down-regulated OX8 Ab-induced CD8 expression. To investigate how NO regulates CD8 expression on PMC, we examined the cGMP-dependent pathway using 8-bromo-cGMP (2 mM) and the guanylate cyclase inhibitor, 1H-oxadiazoloquinoxalin-1-one (20 µM). 8-Bromo-cGMP up-regulated CD8 expression, whereas 1H-oxadiazoloquinoxalin-1-one down-regulated its expression. Thus, ligation of CD8 up-regulates CD8 expression on PMC, a response mediated at least in part by NO through a cGMP-dependent pathway. The significance of this up-regulation of CD8 on mast cells (MC) is unclear, but since ligation of CD8 on MC with OX8 Ab can alter gene expression and mediator secretion, up-regulation of CD8 may enhance the MC response to natural ligation of this novel form of CD8.

This article has been cited by other articles:

				P. Forsythe and A. D. Befus Inhibition of Calpain Is a Component of Nitric Oxide-Induced Down-Regulation of Human Mast Cell Adhesion J. Immunol., January 1, 2003; 170(1): 287 - 293. [Abstract] [Full Text] [PDF]