Differential production of leukotriene B4 or prostaglandin E2 by WKYMVm or serum amyloid A via formyl peptide receptor-like 1

Serum amyloid A (SAA) and Typ-Lys-Tyr-Met-Val-D-Met (WKYMVm) have been reported as formyl peptide receptor-like 1 (FPRL1) ligands. WKYMVm but not SAA stimulated superoxide generation by human neutrophils. In terms of the downstream signalings triggered by WKYMVm and SAA, both agonists stimulated cytosolic phospholipase A(2)-mediated arachidonic acid release, a precursor of leukotriene B4 (LTB4) and prostaglandin E-2 (PGE(2)). WKYMVm also strongly stimulated LTB4 production in human neutrophils without affecting PGE(2) production, whereas SAA strongly stimulates cyclooxygenase-2 (COX-2) expression and PGE(2) production but not LTB4 production. In terms of the receptors responsible for the differential actions of these two agonists, we found that FPRL1 is involved in the production of LTB4 by WKYMVm and PGE(2) production by SAA. This study demonstrates that the chemoattractant receptor, FPRL1, can be differentially regulated by distinct ligands to generate different lipid mediators, and thus, different immune responses. (c) 2006 Elsevier Inc. All rights reserved.