Platelet-activating factor-induced human eosinophil transendothelial migration: evidence for a dynamic role of the endothelium.
Stimulated migration of eosinophils out of the bloodstream and into the lung is key in the development of tissue eosinophilia and inflammation in asthma. Platelet-activating factor (PAF) has been implicated as an important inflammatory mediator in asthma pathogenesis in part because of its chemotactic capacity. We therefore studied the ability of PAF to induce human peripheral blood eosinophil migration through naked filters and human umbilical vein endothelial cells (HUVECs) cultured on these filters. PAF induced eosinophil migration through both barriers in a time-dependent fashion, with maximal eosinophil migration occurring at 180 min. Significant eosinophil migration was observed at PAF concentration > or = 0.1 microM and was dose dependent up to 10.0 microM. No significant differences in eosinophil chemotactic responses were noted between naked filter and HUVEC barriers. The PAF receptor antagonist, WEB 2086, inhibited (> 85%) eosinophil transendothelial migration when co-incubated with PAF or when used as a pretreatment of either the eosinophils or HUVECs. However, WEB 2086 pretreatment of HUVECs did not inhibit PAF-induced neutrophil transendothelial migration, nor did it affect leukotriene B4-induced neutrophil or eosinophil transendothelial migration. Thus, the data indicate that the endothelial cell plays an important role in PAF-induced eosinophil inflammatory processes. Moreover, these data suggest that PAF's pathogenic role in asthma may in part be due to its ability to stimulate eosinophil migration across endothelial barriers and into the airways.
Casale
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242-1009.
Erger
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Little
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D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D004804:Eosinophils / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D008854:Microscopy, Electron; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D007975:Leukotriene B4