Modulation of platelet-activating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMN): role of extracellular albumin.
Human neutrophilic polymorphonuclear leukocytes (PMN) stimulated with N'-formyl-methionyl-leucyl-phenylalanine (FMLP) in the presence of cytochalasin B but in the absence of human serum albumin (HSA) synthesized only small amounts of platelet-activating factor (PAF) that attained maximum levels within 60-120 s after stimulation; in addition, no release of PAF occurred. However, in the presence of 2.5 mg HSA/ml, there was a threefold increase in PAF synthesis, 30-40% of which was released within 5 min after FMLP stimulation. In the presence of 50 mg HSA/ml there was at least a fourfold increase in PAF synthesis and release, with maximal synthesis occurring 10-20 min after stimulation. Thus, the presence of HSA during PMN stimulation not only induced an albumin dose-dependent increase in PAF release but significantly augmented the synthesis of PAF. In contrast to PAF synthesis and release, the presence or absence of HSA had no effect upon lysosomal enzyme secretion from FMLP-stimulated PMN, which was maximal within 30-60s after stimulation. These results demonstrate that HSA plays an essential role in vitro in the synthesis and release of PAF from human PMN, and support the hypothesis that there is a cyclic PAF synthesis-release coupling mechanism in the stimulated human PMN.
D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000302:isolation & purification; D012709:Serum Albumin / Q000494:pharmacology*; D014316:Tritium
D010972:Platelet Activating Factor; D012709:Serum Albumin; D014316:Tritium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium