Platelet-activating factor in inflammation and pulmonary disorders.

Since its recognition as a substance released from rabbit basophils after IgE stimulation that is capable of causing platelet aggregation [ 1, 21, plateletactivating factor (PAF, l-alkyl-2-acetyl-sn-glycero-3phosphocholine) has continued to generate interest as a potent mediator of inflammation. Compared with other lipid mediators of inflammation, such as those generated from the cyclo-oxygenase or lipoxygenase pathways, PAF has a wider range of inflammatory effects on many cell types, such as activation of neutrophils, eosinophils, lymphocytes and macrophages, increased adherence of various inflammatory cells to the vascular endothelium, inducing microvascular leakage, and ‘priming’ of inflammatory cells. Within a few years of its discovery, PAF was implicated as a mediator of inflammation in various diseases with a chronic inflammatory component. With respect to diseases of the lungs, asthma has figured prominently, but PAF has also been implicated in pulmonary hypertension and the adult respiratory distress syndrome (ARDS). The recent availability of specific, potent PAF antagonists has given further impetus to the investigation of the role of PAF in these conditions [3, 41. Coupled with this opportunity for the investigation of the role of PAF in disease, there are increasing new data on the biological actions of PAF, including a potential intracellular role and its interactions with cytokines which indicate the complexity of any potential role for PAF in health and disease. Several reviews have already been published on the subject of PAF [5-91; in this review, I will bring together some of the more recent observations, including the potential effects of PAF antagonists in pulmonary disease. METABOLISM OF PAF