Interferon-gamma, bacterial lipopolysaccharide, and tumor necrosis factor-alpha induce CD11a mRNA and protein via Na+/H+ exchange and protein kinase C dependent mechanisms in tissue macrophages

Previously CD11a or leukocyte function-associated antigen alpha-1 was found to be induced at the surface protein level in thioglycolate-elicited perit oneal macrophages by bacterial lipopolysaccharide and interferon-gamma. To investigate this induction further, Northern blotting and enzyme-linked imm unosorbent assays were used to examine the role of second messengers in CD1 1a gene product induction by these agents. Here I report that CD11a RNA and cell surface protein induced by bacterial lipopolysaccharide and tumor nec rosis factor-alpha are sensitive to inhibition of protein kinase C, while i nsensitive to inhibition of Na+/H+ exchange. CD11a induction by interferon- gamma conversely is sensitive to inhibition of Na+/H+ exchange and insensit ive to inhibition of protein kinase C. These observations indicate that CD1 1a may be induced by multiple and separate second messenger systems in prim ary macrophages. (C) 1999 Academic Press.