SCAVENGER RECEPTORS MAY REGULATE NITRIC-OXIDE PRODUCTION FROM MACROPHAGES STIMULATED BY LPS

The effects of scavenger receptor (SR) ligands on nitric oxide (NO) pr oduction were investigated using mouse peritoneal macrophages stimulat ed by LPS. Pretreatment of macrophages with oxidized LDL, heparin, mal eylated BSA, or liposomes composed of phosphatidylserine (PS-liposomes ) inhibited NO production, but native LDL, acetyl LDL dextran sulfate, did not. Immunoblotting analysis suggests that the inhibitory effects could be a result of the inhibition of inducible NO synthase (iNOS) i nduction, but not enzyme activity. Further, tyrosine phosphorylation o f a 41 kDa protein was also inhibited by OxLDL, heparin, maleylated BS A, and PS-liposomes. Chloroquine did not affect the extent of inhibiti on of NO production induced by these ligands, suggesting that the bind ing of these ligands to SR generates a signal(s) which is involved in the inhibition of NO production from macrophages stimulated by LPS. SR , which has an affinity to these ligands, may strictly regulate NO pro duction from macrophages, and this inhibitory effect may be due to the inhibition of LPS-induced tyrosine phosphorylation of 41 kDa protein. (C) 1997 Academic Press.