Suppression of macrophage Ia antigen expression by endogenous interferon-alpha/beta.
Exogenous interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) (type I IFNs) are known to suppress the IFN-gamma-dependent expression of class II MHC (Ia) antigens on macrophages (M phi). We report here that the endogenous type I IFNs produced by M phi in response to IFN inducers regulate Ia expression of the M phi themselves. Coculture of M phi with IFN-gamma and polyinosinic-polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression in comparison with those cultured without poly(I):poly(C). Pretreatment of M phi with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a potent IFN inducer, in vitro or in vivo, before being exposed to IFN-gamma was also effective in suppressing the Ia expression. Such suppression was abolished by the addition of anti-IFN-alpha/beta antibodies to the M phi culture along with IFN-gamma. M phi cultured with L-cell conditioned medium (LCM) containing M-CSF were less capable of expressing Ia antigens than those cultured without LCM. The Ia-expressing ability of LCM-treated M phi was also restored by the addition of anti-IFN-alpha/beta antibodies. M phi in the early stage of sterile inflammation were less responsive to IFN-gamma than those in the late stage. These results suggest that endogenous type I IFNs, which are produced in response to natural or synthetic IFN-inducers, regulate M phi Ia expression in an autocrinal manner.
Kato
T
T
Department of Zoology, Faculty of Science, Kyoto University.
Kitaura
M
M
Inaba
K
K
Watanabe
Y
Y
Kawade
Y
Y
Muramatsu
S
S
D000818:Animals; D015152:Blotting, Northern; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000097:blood*; D007249:Inflammation / Q000473:pathology; D007369:Interferon Inducers / Q000494:pharmacology; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000737:chemistry / Q000378:metabolism; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011070:Poly I-C / Q000494:pharmacology; D012313:RNA / Q000302:isolation & purification; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic / Q000494:pharmacology / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D007369:Interferon Inducers; D007370:Interferon Type I; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic; D012313:RNA; D007371:Interferon-gamma; D011070:Poly I-C