Modulation of macrophage Ia-expression by lipopolysaccharide. I. Induction of Ia expression in vivo.
Experiments were performed to analyze the modulation of macrophage Ia expression and biosynthesis by Salmonella minnesota-derived lipopolysaccharide (LPS) in vivo. The i.p. injection of LPS into LPS-responder mice caused a dramatic increase in the Ia expression of the peritoneal macrophage population harvested 1 wk after injection. As little as 1 ng of lipid-rich Re595 LPS per mouse caused a significant I-Ak increase, and 1 microgram was optimal; wild-type S. minnesota LPS was less active. No I-Ak induction by LPS was observed in the LPS-nonresponder strain C3H/HeJ. LPS-induced macrophages showed a 6- to 16-fold increase in I-Ak expression by radioimmunoassay (RIA), a 3- to 10-fold increase in the proportion of I-Ak-positive cells, and a 10- to 15-fold increase in I-Ak biosynthetic capacity. The magnitude of this induction by LPS was comparable to increases observed after injection of live Listeria monocytogenes. The kinetics of I-Ak induction by LPS and by L. monocytogenes were different: LPS caused an initial decrease in I-Ak expression 1 day after injection, and I-Ak induction by LPS occurred more slowly and maintained heightened expression longer. Several H-2 gene products (H-2Kk, I-Ak, and I-Ek) were augmented in LPS-induced macrophages. In keeping with increased I-A and I-E expression, LPS-induced macrophages were more effective than normal macrophages in presenting antigen to T lymphocytes. We suggest that the modulation of macrophage Ia expression is one important mechanism contributing to the immunoregulatory activity of LPS.
D000818:Animals; D001202:Ascitic Fluid / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D014176:Protein Biosynthesis; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides