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.
Immunology Section/DMIPP/IPTSP, Federal University of Goiás, Goiânia, Brazil.
Fátima
F
Ribeiro-Dias
Marina Tiemi
MT
Shio
Jorge
J
Timenetsky
Ana Paula Camilo
AP
Oliane
Camila Cardoso
CC
Metran
Fábio Borges
FB
Pessoa
Sonia
S
Jancar
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