The Role of Platelet-Activating Factor in the Biocompatibility of Hemodialysis Membranes

Abstract

Extracorporeal treatments for acute or chronic replacement of organ function still represent a challenge for today’s technology. Activation of fluid phase (complement, coagulation, fibrinolysis) and cellular systems (leukocytes, platelets) is known to occur in hemodialysis (1). Among other biochemical indications of leukocyte activation as a conseguence of blood-surface interactions such as oxygen radicals, release of granulocyte proteinases, monocyte prostaglandin release and cytokine generation, platelet-activating factor (PAF) has drawn interest in various biocompatibility studies (reviewed in 1–5). PAF is a phospholipid mediator of inflammation with different biologic properties relevant for the development of inflammation and septic shock (7–11). PAF may act at concentrations of 10⁻¹²M and requires an ether linkage at the sn-1 position of the glycerol backbone, a short acyl chain, usually an acetyl residue, at the sn-2 position, and the polar head group of choline or ethanolamine at the sn-3 position (7–8). However, it has been shown recently that PAF belongs to a family of structurally related phospholipid molecules of biologic origin that shares many physiologic activities (12). PAF is considered a mediator of cell-to-cell communication that may function both as an intracellular and intracellular messenger. PAF is produced after immunologic or nor immunologic challenge by a variety of cells such as monocytes/macrophages, polymorphonuclear neutrophils, basophils and platelets, that may participate in the development of inflammatory reaction (13). In addition, human endothelial cells were found to produce PAF after stimulation by several inflammatory mediators including thrombin, angiotensin II, vasopressin, leukotriene C4 and D4, histamine, bradykinin, elastase, catheprin G, and plastic (14–18). PAF acts in an autocrine and paracrine way through a specific receptor for which a cDNA has been cloned (19,20). The receptor belongs to the family of “serpentine” receptors containing sever a-helical domains that weave in and out plasma membrane and it interacts with a G protein, which activates a phosphatidylinositol-specific phospholipase C (19,20). PAF receptors exist in all cells that are known targets for PAF. Recently, also human cultured endothelial cells have been shown to express PAF receptors (21). PAF promotes the permeability of the EC monolayer leading to cell retraction and formation of intracellular gaps (22). PAF induces in vitro migration of endothelial cells and promotes in vivo angiogenesis by a heparin-dependent mechanism (21). The aim of the present review is to briefly summarize early evidence for a role of PAF in bioincompatibility events and to highlight recent advances and their possible potential practical application in testing polymer biocompatibility.