Dobrina A, Menegazzi R, Carlos T M, Nardon E, Cramer R, Zacchi T, Harlan J M, Patriarca P
Institute of General Pathology, University of Trieste, Italy.
J Clin Invest. 1991 Jul;88(1):20-6. doi: 10.1172/JCI115278.
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.
我们研究了在三种条件下正常外周血嗜酸性粒细胞与培养的人脐静脉内皮细胞（HEC）黏附所涉及的机制：（a）在未用激活剂处理HEC或嗜酸性粒细胞的情况下的黏附（基础黏附）；（b）用佛波酯刺激嗜酸性粒细胞诱导的黏附（嗜酸性粒细胞依赖性黏附）；以及（c）用脂多糖（LPS）、肿瘤坏死因子（TNF）或白细胞介素-1（IL-1）预处理HEC诱导的黏附（内皮细胞依赖性黏附）。我们确定了一种在基础黏附、嗜酸性粒细胞依赖性黏附和内皮细胞依赖性黏附中均同样活跃的机制。该机制在同时存在Ca++和Mg++时活性最佳，而仅存在Ca++或仅存在Mg++时活性降低。此外，与嗜酸性粒细胞黏附的其他机制一样，它在37℃时活跃，但在4℃时不活跃。第二种黏附机制参与嗜酸性粒细胞依赖性黏附和内皮细胞依赖性黏附。该机制依赖于嗜酸性粒细胞的CD11/CD18黏附复合体（即被抗CD18单克隆抗体抑制），并且在存在Ca++和Mg++或仅存在Mg++时活跃，但仅存在Ca++时不活跃。第三种黏附机制特定于内皮细胞依赖性黏附。它涉及内皮细胞配体血管细胞黏附分子-1（VCAM-1）和嗜酸性粒细胞受体极迟活化抗原-4（VLA-4，CD49d/CD29，即被抗VCAM-1单克隆抗体或抗VLA-4单克隆抗体抑制）。该机制在存在Ca++和Mg++时活跃，但仅存在Ca++或仅存在Mg++时不活跃，并且在用佛波酯刺激嗜酸性粒细胞时不会上调或下调。相反，结合中性粒细胞和单核细胞的内皮白细胞黏附分子-1（ELAM-1）不参与嗜酸性粒细胞与LPS、TNF或IL-1刺激的HEC的黏附（即不被抗ELAM-1单克隆抗体抑制）。我们得出结论，嗜酸性粒细胞与单核细胞和淋巴细胞一样，通过整合素受体VLA-4与细胞因子诱导的内皮细胞配体VCAM-1结合。
