Polymorphonuclear leukocyte-platelet interactions: acetylglyceryl ether phosphocholine-induced platelet activation...

A mixture of rabbit polymorphonuclear leukocytes (PMNs) and platelets at concentrations of 5 X 10(6) PMN and 3.5 X 10(8) platelets/ml Tyrode's solution was stimulated with the chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP). A micromolar concentration of FMLP elicited an immediate weak aggregation, followed by a strong aggregation with a time lag of about 1 min. Microscopic examination showed that the immediate aggregation was due to PMNs and the delayed one was more complex and involved platelets. The delayed aggregation was dependent upon the concentrations of both the PMNs and FMLP. The delayed aggregation was completely blocked by pretreatment of the PMN-platelet mixture with 8 microM CV-3988, a specific receptor antagonist of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC), or by the application of platelets desensitized to AGEPC. The time course of AGEPC production by PMNs was well matched to that of the biphasic aggregation response. Furthermore, nordihydroguaiaretic acid inhibited both the AGEPC production by PMNs and the delayed aggregation in a similar dose-dependent manner. These result demonstrate that AGEPC, newly-generated by PMNs under FMLP-stimulation, is of primary importance in platelet aggregation in a PMN-platelet mixed system.