MECHANISMS OF EOSINOPHIL ADHERENCE TO CULTURED VASCULAR ENDOTHELIAL-CELLS - EOSINOPHILS BIND TO THE CYTOKINE-INDUCED ENDOTHELIAL LIGAND VASCULAR CELL-ADHESION MOLECULE-1 VIA THE VERY LATE ACTIVATION ANTIGEN-4 INTEGRIN RECEPTOR

被引:290
作者
DOBRINA, A
MENEGAZZI, R
CARLOS, TM
NARDON, E
CRAMER, R
ZACCHI, T
HARLAN, JM
PATRIARCA, P
机构
[1] UNIV WASHINGTON,DEPT MED,DIV HEMATOL,ROOM 10,SEATTLE,WA 98195
[2] UNIV TRIESTE,INST GEN PATHOL,I-34127 TRIESTE,ITALY
[3] CARLO & DIRCE CALLERIO FDN,I-34127 TRIESTE,ITALY
关键词
VASCULAR CELL ADHESION MOLECULE-1; VERY LATE ACTIVATION ANTIGEN-4; EOSINOPHIL; ENDOTHELIUM; ADHERENCE;
D O I
10.1172/JCI115278
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
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页码:20 / 26
页数:7
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