Biochemistry of Platelet-Activating Factor: A Unique Class of Biologically Active Phospholipids 1

Abstract

Abstract

I. Introduction

In the autumn of 1979, three independent laboratories (1–3) described the chemical structure of a new subclass of phospholipids that possessed biologic properties identical to platelet-activating factor (PAF) and an antihypertensive polar renal lipid (APRL). The chemical features of this unique bioactive phospholipid are an O-alkyl ether group at the sn-1 position, an acetate at the sn-2 position, and a phosphocholine moiety at the sn-3 position of the sn-glycerol moiety (Fig. 1). A number of reviews have provided a detailed account of earlier developments in the PAF (4–11) and APRL (10, 12) fields and, therefore, only significant historical events are highlighted in this section.

The antihypertensive activity of an extract from the renal medulla was originally observed in dogs with renoprival hypertension (13). This antihypertensive principle could also be extracted from renomedullary interstitial cells of rats and was initially referred to as ARH, an antihypertensive renomedullary hormone (14). However, further characterization of the polar nature of this lipid led to changing the name of ARH to APRL, the abbreviation for antihypertensive polar renomedullary lipid (15).

Within the same time frame of the APRL investigations, several articles (16–18) appeared which described the release of vasoactive amines from rabbit platelets in a reaction that required leukocytes from an immunized rabbit, an antigen, and platelets; the reaction, referred to as leukocyte-dependent release of histamine (LDHR), was considered as an immediate hypersensitivity-type reaction linked to allergic responses. Benveniste et al. (19) further characterized this soluble factor and identified IgE-stimulated basophils as the source of the substance responsible for LDHR and the aggregation of platelets; these workers called the bioactive substance PAF. The lipid nature and polar properties of PAF finally became apparent from chemical studies of its solubility characteristics, chromatographic behavior on silicic acid, and reactivity with lipases (20, 21).