MALEYLATED-BSA ENHANCES PRODUCTION OF NITRIC-OXIDE FROM MACROPHAGES

Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion of a number of proinflammatory genes via ligation of the lo w-affinity scavenger receptor (SR) on macrophages. We now demonstrate that while neither maleyl-BSA, nor interferon-gamma (INF-gamma) alone induce nitric oxide (NO) production, when combined they promote releas e of NO from murine peritoneal macrophages. This effect was blocked by treatment with oxidized-low density lipoprotein. Maleyl-BSA activated NF-kappa B dimers capable of binding the NF-kappa Bd sequence unique to the iNOS promoter, but this failed to induce significant new transc ription or accumulation of iNOS mRNA. The combination of maleyl-BSA an d IFN-gamma failed to demonstrate synergy at the transcriptional or mR NA levels, as these levels were comparable to those elicited by IFN-ga mma alone. These studies suggest that the synergy in NO production bet ween maleyl-BSA and IFN-gamma occurs after the accumulation of iNOS-sp ecific mRNA, possibly at the translational or post-translational level . (C) 1998 Academic Press.