1-O-ALKYL-SN-GLYCERYL-3-PHOSPHORYLCHOLINES - A NOVEL CLASS OF NEUTROPHIL STIMULANTS

Abstract

1-O-Alkyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine aggregates and degranulates platelets and polymorphonuclear neutrophils. The bioactivities of this platelet-activating factor, its 2-O-ethyl and its 2-lyso derivatives were examined. Each phospholipid aggregated and degranulated rabbit platelets and neutrophils with relative potencies of .apprx. 10,000, 1000 and 1, respectively. For rabbit neutrophils, the 2-O-acetyl compound was active in nanomolar and lower concentrations; required extracellular Ca and Mg to induce aggregation; and required extracellular Ca and cytochlasin B to induce optimal degranulation. The 2-O-acetyl and 2-O-ethyl compounds, in concentrations .apprx. 10-fold higher than those required for rabbit neutrophils, aggregated and degranulated human neutrophils. With reference to these human neutrophil responses, degranulation required and aggregation was dramatically enhanced by cytochalasin B. The lyso analog was unable to induce these responses in the human cells. The lipids represent a novel class of neutrophil stimulants that closely resemble certain chemotactic factors (e.g., C5a [fragment a of complement component 5] and synthetic oligopeptides) in their ability to aggregate and degranulate neutrophils and in the influences which Ca, Mg and cytochalasin B have on their bioactions. As platelet-activating factor circulates in the blood of rabbits and humans during anaphylaxis and is suspected of being involved in other syndromes, i.e., serum sickness, this lipid may have unique biologic significance: it may act to recruit platelets and neutrophils into the lesions of these and similar pathologic syndromes.