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

Am J Respir Cell Mol Biol. 1997 Aug;17(2):181-92. doi: 10.1165/ajrcmb.17.2.2818.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Cells, Cultured
  • Chemokine CXCL5
  • Chemokines, CXC*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / pharmacology
  • Interleukin-8 / analogs & derivatives*
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Lung / metabolism
  • Neutrophils / cytology*
  • Signal Transduction*


  • CXCL5 protein, human
  • Chemokine CXCL5
  • Chemokines, CXC
  • Interleukin-1
  • Interleukin-8