Engagement of major histocompatibility complex class II molecules leads to nitrite production in bone marrow-derived macrophages.
The present study was designed to examine whether engagement of major histocompatibility complex (MHC) class II molecules can lead to induction of NO synthase in bone marrow-derived macrophages. We treated the macrophages with toxic shock syndrome toxin 1 (TSST-1), a superantigen which activates T cells in an MHC class II-dependent manner. Upon addition of syngeneic spleen cells as a source of mature T cells to the TSST-1-treated macrophage culture. NO2- production was greatly increased. To test whether monoclonal antibodies (mAb) to MHC class II antigens also serve as an effective trigger signal for induction of NO synthase we incubated the cells with the anti-I-Ad/b mAb D3.137 and measured NO2- production in culture supernatants. The addition of the mAb D3.137 resulted in NO2- production which was completely suppressed by NG-monomethyl-L-arginine, a homologue of L-arginine, indicating that antibody-induced NO2- production was due to activation of NO synthase. The ability of anti-I-A antibodies, which may imitate the effects of T cells, to induce NO2- production suggests that MHC class II molecules act as transmembrane signal transducers finally leading to induction of NO synthase.
Hauschildt
S
S
Institut für Immunobiologie, Universität Freiburg, FRG.
Bessler
W G
WG
Scheipers
P
P
D000470:Alkaloids / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001427:Bacterial Toxins; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells; D004768:Enterotoxins / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006358:Hot Temperature; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D011112:Polymyxin B / Q000494:pharmacology; D019311:Staurosporine; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D009569:Nitric Oxide; C031818:enterotoxin B, staphylococcal; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019311:Staurosporine; D011112:Polymyxin B