THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-ALPHA (PPAR-ALPHA) LIGAND WY-14,643 DOES NOT INTERFERE WITH LEUKOTRIENE B4 INDUCED ADHESION OF NEUTROPHILS TO ENDOTHELIAL-CELLS

Peroxisome proliferator-activated receptors (PPAR) control discrete ge nes involved in fatty acid and lipid metabolism. Recently, it was sugg ested that activation of the alpha isoform of PPAR by the potent proin flammatory mediator leukotriene B-4 (LTB4) enhanced degradation of thi s eicosanoid, offer suggesting a new aspect of down-regulation of infl ammation. Here, we studied whether PPAR alpha activation (by means of the selective agonist WY 14,643) of endothelial cells, pivotal in the regulation of inflammatory responses, interfered with LTB4 induced adh esion of PMN neutrophil granulocytes in vitro. when endothelial cells were treated with WY 14,643 prior to activation with LTB4 (or fMLP, IL -1 beta or TNF alpha, as controls) we could not document any effect on the number of adhering PMN or duration of the response. Thus, this st udy provides no evidence indicating a regulatory function of PPAR alph a in LTB4 induced adhesive interactions between endothelial cells and neutrophils. (C) 1998 Academic Press.