Evidence for the involvement of macrophage-derived nitric oxide in the modulation of immune status by a conditioned aversive stimulus.
Prior work in our laboratory has demonstrated that exposure to a conditioned aversive stimulus developed through pairings with electric shock results in pronounced alterations of immune status. These conditioned alterations of immune status include a decreased in natural killer cell activity, decreased production of interleukin-2 and gamma-interferon by concanavalin A (ConA)-stimulated splenocytes and a profound suppression of the mitogenic responsiveness of T and B lymphocytes to mitogens. The present study examines the role of macrophage-derived nitric oxide in the conditioned stimulus-induced suppression of lymphocyte proliferation by measuring the level of nitrite accumulation in culture, determining the effect of macrophage depletion, and assessing the effect of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of the L-arginine-dependent nitric-oxide synthesizing pathway, alone and in combination with L- or D-arginine. The results show that the conditioned suppression of the mitogenic responsiveness of splenocytes to ConA is accompanied by a marked increase in nitrite accumulation. Both the depletion of macrophages and the addition of L-NMMA attenuates the conditioned suppression of ConA-stimulated lymphocyte proliferation. Furthermore, the addition of excess L-arginine, but not D-arginine, counteracts the effect of L-NMMA. The present findings show that the neuroendocrine alterations induced by a conditioned aversive stimulus suppress lymphocyte proliferation through alteration of the production of nitric oxide by macrophages.
Coussons-Read
M E
ME
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
Maslonek
K A
KA
Fecho
K
K
Perez
L
L
Lysle
D T
DT
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D003213:Conditioning, Psychological; D004597:Electroshock; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D019323:omega-N-Methylarginine
D003208:Concanavalin A; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine