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Am J Respir Cell Mol Biol. 1997 Aug;17(2):181-92.

Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion.

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The Nora Eccles Harrison Cardiovascular Research and Training Institute, and the Department of Anatomy, University of Utah Health Sciences Center, Salt Lake City 84112, USA.


The interaction of endothelial cells and polymorphonuclear leukocytes (PMNs, neutrophils) is a critical determinant of the acute inflammatory response, and mirrors cell-cell interactions in other biologic systems. Adhesion molecules that tether the two cells together, and signaling factors that bind to receptors on the leukocytes and mediate their spatially-localized activation, govern PMN responses as they adhere to and traverse stimulated endothelial cells. Here we show that cultured human endothelial cells express two members of the C-X-C family of chemokines, epithelial neutrophil activating peptide-78 (ENA-78) and interleukin (IL)-8, when stimulated by IL-1 or certain other agonists. ENA-78, previously thought to be exclusively a product of epithelium, is expressed by in situ endothelium in inflamed human lung and other tissues as well as by cultured endothelial cells. The regulation of ENA-78 and IL-8 share certain features in common and they have overlapping biologic activities, including the ability to induce PMN adhesiveness. This was demonstrated in experiments in which we found that ENA-78 induces inside-out signaling of beta2 integrins on the PMN surface, as does IL-8. Antibody blocking experiments demonstrated that ENA-78 contributes to the proadhesive activity for neutrophils that is released by endothelial cells stimulated with IL-1 for a prolonged period and that it acts in concert with IL-8, which provides the major component of the signal for adhesion under this condition. We also show, however, that the temporal expression and secretion of ENA-78 and other characteristics of its handling by stimulated endothelial cells vary from the expression of IL-8, indicating that differential regulation of the two signaling chemokines occurs in this cell type.

[Indexed for MEDLINE]

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