Mechanisms of eosinophil adherence to cultured vascular endothelial cells. Eosinophils bind to the cytokine-induced ligand vascular cell adhesion molecule-1 via the very late activation antigen-4 integrin receptor.
We have examined the mechanisms involved in the adherence of normal peripheral blood eosinophils to cultured human umbilical vein endothelial cells (HEC) under three conditions: (a) adherence in the absence of treatment of HEC or eosinophils with activating agents (basal adherence); (b) adherence induced by stimulation of eosinophils with phorbol ester (eosinophil-dependent adherence); and (c) adherence induced by pretreatment of HEC with LPS, tumor necrosis factor (TNF), or IL-1 (endothelial-dependent adherence). A mechanism was identified that was equally active in basal, eosinophil-dependent, and endothelial-dependent adherence. This mechanism was optimally active in the presence of both Ca++ and Mg++, and reduced in the presence of Ca++ only or Mg++ only. Furthermore, like the other mechanisms of eosinophil adherence, it was active at 37 degrees C but not at 4 degrees C. A second mechanism of adherence was involved in eosinophil- and in endothelial-dependent adherence. This mechanism was dependent on the CD11/CD18 adhesion complex of eosinophils (i.e., inhibited by anti-CD18 MAb) and it was active in the presence of Ca++ and Mg++ or Mg++ only, but not Ca++ only. The third mechanism of adherence was specific for endothelial-dependent adherence. It involved the endothelial ligand vascular cell adhesion molecule-1 (VCAM-1) and the eosinophil receptor very late activation antigen-4 (VLA-4, CD49d/CD29, i.e., inhibited by anti-VCAM-1 MAb or anti-VLA-4 MAb). This mechanism was active in the presence of Ca++ and Mg++ but not of Ca++ only or Mg++ only, and was not up- or downregulated when eosinophils were stimulated with phorbol ester. In contrast, the endothelial leukocyte adhesion molecule-1 (ELAM-1), that binds neutrophils and monocytes, was not involved in eosinophil adherence to LPS-, TNF-, or IL-1-stimulated HEC (i.e., not inhibited by anti-ELAM-1 MAb). We conclude that eosinophils, like monocytes and lymphocytes, bind to the cytokine-induced endothelial ligand VCAM-1 via the integrin receptor VLA-4.
Dobrina
A
A
Institute of General Pathology, University of Trieste, Italy.
Menegazzi
R
R
Carlos
T M
TM
Nardon
E
E
Cramer
R
R
Zacchi
T
T
Harlan
J M
JM
Patriarca
P
P
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D018821:CD18 Antigens; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology*; D004804:Eosinophils / Q000502:physiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D016029:Receptors, Very Late Antigen / Q000502:physiology*; D013696:Temperature; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D008070:Lipopolysaccharides; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D008274:Magnesium; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium