Mycoplasma arthritidis superantigen (MAM)-induced macrophage nitric oxide release is MHC class II restricted, interferongamma dependent, and toll-like receptor 4 independent.
Mycoplasma arthritidis causes arthritis in rodents that resembles human rheumatoid arthritis. It produces a superantigen (MAM) that stimulates production of cytokines by making a bridge between lymphocyte T-cell receptor with the appropriate Vbeta chain, and H-2 1-Ealpha MHC class II molecules. Here we studied MAM-induced nitric oxide (NO) production in mouse peritoneal macrophages and found that it was: (1) time and concentration dependent, (2) possibly derived from inducible NOS synthase since it was reduced significantly by amino guanidine pretreatment, (3) restricted to H-2(K) (C3H/HePas and C3H/HeJ) and H-2(d) strains (BALB/c), (4) independent of TLR4 signaling since the coisogenic strains C3H/HePas and C3H/HeJ (TLR4 deficient) produced similar levels of NO following MAM stimulation, (5) potentiated by lipopolysaccharide, and (6) dependent on the presence of nonadherent peritoneal cells. Neutralization of interferon-gamma (IFNgamma in the peritoneal cell cultures with monoclonal antibodies abolished MAM-induced NO production. Addition of rIFNgamma to the adherent cells substituted the nonadherent cells for MAM-induced NO production. A macrophage cell line, J774A.1 (H-2(d)), also produced NO upon MAM stimulation but only when BALB/c spleen lymphocytes were added. Thus, in murine macrophages, MAM induces NO production that is dependent on signaling through MHC class II molecules and IFNgamma but independent of TLR4 expression.
Ribeiro-Dias
Fátima
F
Immunology Section/DMIPP/IPTSP, Federal University of Goiás, Goiânia, Brazil.
Shio
Marina Tiemi
MT
Timenetsky
Jorge
J
Oliane
Ana Paula Camilo
AP
Metran
Camila Cardoso
CC
Pessoa
Fábio Borges
FB
Jancar
Sonia
S
D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D011506:Proteins; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D018089:Superantigens; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000941:Antigens; D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D011956:Receptors, Cell Surface; D018089:Superantigens; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase