In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil-endothelial adhesive interactions

J Immunol. 1992 Sep 15;149(6):2163-71.

Abstract

We have previously reported that cytokine- or LPS-activated human umbilical vein endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil-selective adhesion inhibitor. In our study we investigated the mechanisms involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte adhesion inhibitory effect appears to be mediated by the action of IL-8 on the neutrophil, does not involve down-regulation of relevant endothelial adhesion molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular adhesion molecule-1, and is quantitatively similar in different endothelial activation states that are predominantly endothelial-leukocyte adhesion molecule-1 dependent or intercellular adhesion molecule-1 dependent. In addition to inhibiting the attachment of freshly isolated peripheral blood neutrophils to cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of tightly adherent neutrophils from activated HUVEC, and abolished neutrophil transendothelial migration. Certain other chemoattractants, including FMLP and C5a, had similar inhibitory actions, indicating IL-8 was not unique in its ability to inhibit various neutrophil-endothelial interactions. In contrast, two other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal inhibitory effects on adhesion. Regardless of their ability to modulate neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte surface expression of functionally important adhesion molecules, including loss of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in CD11b/CD18. Thus, although the above agonists have been characterized primarily as chemoattractants, our findings demonstrate that these agents can exert a wide range of modulatory effects on neutrophil-endothelial adhesive interactions.

Publication types

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

MeSH terms

  • Antigens, CD / metabolism
  • CD18 Antigens
  • Cell Adhesion / drug effects*
  • Cell Adhesion Molecules / metabolism
  • Cells, Cultured
  • Chemotactic Factors / pharmacology*
  • Chemotaxis / drug effects
  • Cytokines / pharmacology
  • E-Selectin
  • Endothelium, Vascular / cytology*
  • HLA Antigens / metabolism
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1
  • Interleukin-8 / pharmacology*
  • L-Selectin
  • Macrophage-1 Antigen / metabolism
  • Neutrophils / cytology*

Substances

  • Antigens, CD
  • CD18 Antigens
  • Cell Adhesion Molecules
  • Chemotactic Factors
  • Cytokines
  • E-Selectin
  • HLA Antigens
  • Interleukin-8
  • Macrophage-1 Antigen
  • Intercellular Adhesion Molecule-1
  • L-Selectin