Genetic background determines sensitivity to the inhibitory function of NO on T cell proliferation and the amounts of NO production mediated through IFN-gamma.
Abstract: Nitric oxide (NO) inhibits T cell proliferation. We demonstrate that the action of NO on T cell proliferation is different for Lewis and Brown Norway (BN) rats. Splenocytes from Lewis rats consistently showed higher proliferation against concanavalin A than splenocytes from BN rats did. In contrast, NO production was higher in BN rats than in Lewis rats. A depletion of adherent cells increased proliferation in BN rats to a level similar to that in Lewis rats. Thus NO produced by adherent splenocytes could be considered to inhibit proliferation. The addition of NG-monomethyl-L-arginine, a potent inhibitor of NO production, increased proliferation in Lewis rats, but much less so in BN rats. Similar results were obtained by the addition of anti-interferon (IFN)-gamma. It is surprising that, low doses of sodium nitroprusside, an NO donor, increased proliferation in BN rats but not in Lewis rats. To investigate the mechanism of differential NO production between the two strains, splenocytes were stimulated with IFN-gamma. The early signaling event evaluated by the phosphorylation of Stat-1 was similar in both strains, whereas inducible NO synthase (iNOS) mRNA expression seemed more sustained in BN rats. Thus the differential production of NO might be related to the differential transcriptional regulation of iNOS. Altogether, genetic background might be involved in sensitivity to the inhibitory function of NO for T cell proliferation and NO production.
D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D007376:Interleukin-2; D003208:Concanavalin A; D009569:Nitric Oxide; D007371:Interferon-gamma