Generation of, lipid neutrophil chemoattractant activity by histamine-stimulated cultured endothelial cells.
Endothelial cell-neutrophil interactions are an important aspect of inflammatory responses. Because vascular endothelial cells respond to the inflammatory mediator histamine, these studies determined whether histamine could induce endothelial cells to release substances that affect human neutrophil migration. Cultured bovine and human endothelial cells incubated with histamine released neutrophil chemoattractant activity within 1 min; peak levels were noted in 45 min. Cimetidine, an H2 receptor antagonist, blocked chemoattractant production, whereas diphenhydramine, an H1 receptor antagonist, did not. Cycloheximide did not inhibit release of chemoattractant activity, suggesting de novo protein synthesis was not necessary for its appearance. Extraction with acidified diethyl ether partitioned all neutrophil chemoattractant activity into the organic phase. The lipoxygenase pathway inhibitors, diethylcarbamazine and 5,8,11,14 eicosatetraynoic acid, inhibited generation of this lipophilic chemoattractant activity, whereas indomethacin, a cyclo-oxygenase inhibitor, did not. Resolution of the histamine-induced endothelial cell-derived chemoattractant activity by reverse-phase high pressure liquid chromatography yielded several peaks of chemoattractant activity, none of which co-eluted with leukotriene B4, platelet-activating factor, or two mono-hydroxyeicostetraenoic acids. These findings suggest that endothelial cells release lipid neutrophil chemoattractant activity that may play a role in inflammatory responses associated with histamine.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003513:Cycloheximide / Q000494:pharmacology; D004049:Diethylcarbamazine / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008055:Lipids / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology
D008055:Lipids; D011970:Receptors, Histamine H2; D015117:5,8,11,14-Eicosatetraynoic Acid; D006632:Histamine; D003513:Cycloheximide; D004049:Diethylcarbamazine; D007213:Indomethacin