Degree of platelet activating factor-induced neutrophil migration is dependent upon the molecular species.
Multiple molecular species of platelet activating factor (PAF) are produced as a result of inflammatory processes. PAF-induced neutrophil migration across endothelium is intrinsic to inflammatory responses. We therefore compared the ability of three naturally occurring PAF species (C16:0, C18:0, and C18:1), which only varied at carbon 1, to induce 51Cr-labeled human neutrophil migration across a naked 3-microns pore filter and human umbilical vein endothelial (HUVE) monolayers cultured on these filters. Time-course experiments indicated that all species of PAF tested induced significant neutrophil migration between 15 and 45 min. PAF-induced neutrophil migration through both filters alone and HUVE monolayers occurred at lower doses with C16:0 PAF. The rank order of chemotactic potency for the PAF species was C16:0 greater than C18:0 greater than C18:1 with both filters and endothelium coated filters as barriers. Intrinsic differences in the potency of these PAF molecular species to induce neutrophil chemotaxis were greater when HUVE cells were the barriers vs when filters alone were the barriers. Regardless of the molecular species used, at optimal PAF doses the degree of neutrophil migration through HUVE cells was often greater than that through filters alone. The specific PAF antagonist WEB 2086 inhibited neutrophil migration induced by all three PAF species equally. WEB 2086 pretreatment of the neutrophil or WEB 2086 coincubation with PAF, but not WEB 2086 pretreatment of the HUVE cell monolayers, significantly inhibited (65 to 80%) neutrophil migration. We conclude that the degree of PAF-induced neutrophil migration is dependent upon the molecular species of PAF. Moreover, the barrier through which the neutrophil must migrate appears to be important in influencing the overall chemotactic response to the various PAF species.
Carolan
E J
EJ
Department of Internal Medicine, VA Medical Center, Iowa City, IA.
Casale
T B
TB
D001381:Azepines / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000737:chemistry / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D013329:Structure-Activity Relationship; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086