Human endothelial cells synthesize ENA-78: relationship to IL-8 and to signaling of PMN adhesion.
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.
Imaizumi
T
T
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.
Albertine
K H
KH
Jicha
D L
DL
McIntyre
T M
TM
Prescott
S M
SM
Zimmerman
G A
GA
D000328:Adult; D002478:Cells, Cultured; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D016209:Interleukin-8 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology*; D015398:Signal Transduction
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D007375:Interleukin-1; D016209:Interleukin-8