Immunosuppressive activity induced by nitric oxide in culture supernatant of activated rat alveolar macrophages.
Alveolar macrophages (AM) from normal rats had immunosuppressive activity to mitogen-induced proliferative responses of splenic lymphocytes. We studied the mechanism and the implication of the nitric oxide synthetase pathway in AM-mediated suppression of concanavalin A (Con A)-induced lymphocyte proliferation. The culture supernatant from AM cultures alone did not have immunosuppressive activity to Con A-induced proliferative responses of non-adherent spleen cells (n-ad SC), but the culture supernatant from co-culture of AM and autologous n-ad SC had this activity. Con A-pulsed AM also liberated the immunosuppressive factor. When AM and autologous n-ad SC were cultured separately under the condition that medium could freely communicate, the culture supernatant did not suppress the Con A-induced proliferative response of n-ad SC. This indicated that the immunosuppressive factor was liberated when AM was activated by cell-to-cell contact with n-ad SC. Further, we examined the immunosuppressive activity of the culture supernatant of co-culture of AM and autologous n-ad SC to Con A-induced responses of allogeneic n-ad SC and xenogeneic murine n-ad SC, and allogeneic mixed leucocyte reaction, and found that this culture supernatant could suppress all these proliferative responses. Nitrate (NO2-) synthesis was markedly augmented in the culture supernatants of Con A-pulsed AM and co-culture of AM and n-ad SC. NG-monomethyl-L-arginine (MMA), a specific competitive inhibitor of the nitric oxide synthetase pathway (NOSP), extinguished both NO2- synthesis by AM and AM-mediated immunosuppressive activity. These data suggest that NOSP was important in AM-mediated suppression of Con A-induced lymphocyte proliferation.
Kawabe
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Isobe
K I
KI
Hasegawa
Y
Y
Nakashima
I
I
Shimokata
K
K
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003470:Culture Media; D007108:Immune Tolerance / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000276:immunology
D003470:Culture Media; D009569:Nitric Oxide