Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium.
Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium.
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DOI：
10.4049/jimmunol.142.7.2257
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发表时间：
1989-04
影响因子：
4.4
通讯作者：
F. Luscinskas;A. F. Brock;M. Arnaout;M. Gimbrone
中科院分区：
文献类型：
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作者：
F. Luscinskas;A. F. Brock;M. Arnaout;M. Gimbrone
我们研究了内皮细胞 - 白细胞粘附分子 -1（ELAM -1）以及被命名为CD11/CD18的白细胞表面粘附分子复合物在人多形核白细胞（PMN）与经重组白细胞介素 -1β（rIL -1β）刺激4小时或24小时的培养人内皮细胞（HEC）的粘附中所起的作用。在用针对ELAM -1（单克隆抗体H18/17）以及针对CD11a（单克隆抗体L11）、CD11b（单克隆抗体44）、CD11c（单克隆抗体L29）和CD18（单克隆抗体10F12）的单克隆抗体单独或联合处理后，通过一种定量的体外单层粘附试验来测定PMN与白细胞介素 -1激活的HEC的粘附抑制情况。用单克隆抗体H18/7对激活的HEC进行预处理可使PMN粘附抑制47±8%，而对照单克隆抗体无作用。针对CD11/CD18的单克隆抗体显著阻断PMN与激活的HEC的粘附（抗 - CD11a，抑制40±3%；抗 - CD11b，抑制34±4%；抗 - CD18，抑制78±6%）。单克隆抗体H18/7与各种抗 - CD11/CD18单克隆抗体中的每一种联合使用时，对PMN粘附的抑制作用比任何一种单克隆抗体单独使用时都更强。在rIL -1β处理24小时后，当ELAM -1显著减少但仍观察到PMN粘附增加时，单克隆抗体H18/7对PMN粘附无影响。此时，依赖于CD11/CD18的粘附机制占主导，并且一种依赖于CD11c的机制变得明显（抗 - CD11a，抑制67±4%；抗 - CD11b，抑制45±9%；抗 - CD11c，抑制26±6%；抗 - CD18，抑制97±1%）。总之，PMN与白细胞介素 -1激活的HEC的粘附涉及依赖于CD11/CD18的机制和依赖于ELAM -1的机制，并且这些机制的相对贡献在白细胞介素 -1诱导的HEC激活的不同时间有所不同。在4小时时观察到单克隆抗体H18/7与针对CD11/CD18的单克隆抗体联合使用时的累加阻断作用，这意味着CD11/CD18复合物的成员不作为ELAM -1的必需配体发挥作用。
We have examined the contributions of endothelial-leukocyte adhesion molecule-1 (ELAM-1) and the complex of leukocyte surface adhesion molecules designated CD11/CD18 to the adhesion of human polymorphonuclear leukocytes (PMN) to cultured human endothelial cells (HEC), activated by rIL-1 beta for 4 or 24 h. Inhibition of PMN attachment to IL-1-activated HEC was measured in a quantitative in vitro monolayer adhesion assay, after treatment with mAb directed to ELAM-1 (mAb H18/17), and to CD11a (mAb L11), CD11b (mAb 44), CD11c (mAb L29), and CD18 (mAb 10F12), alone or in combination. Pretreatment of activated HEC with mAb H18/7 inhibited PMN adhesion by 47 +/- 8% whereas control mAb had no effect. CD11/CD18-directed mAb significantly blocked PMN adhesion to activated HEC (anti-CD11a, 40 +/- 3%; anti-CD11b, 34 +/- 4%; anti-CD18, 78+/- 6% inhibition). The combination of mAb H18/7 and each of the various anti-CD11/CD18 mAb resulted in greater inhibition of PMN adhesion than any Mab alone. After 24 h of rIL-1 beta treatment, when ELAM-1 was markedly decreased but elevated PMN adhesion was still observed, mAb H18/7 had no effect on PMN adhesion. At this time, CD11/CD18-dependent adhesive mechanisms predominated and a CD11c-dependent mechanism became apparent (anti-CD11a, 67 +/- 4% inhibition; anti-CD11b, 45 +/- 9%; anti-CD11c, 26 +/- 6%; anti-CD18, 97 +/- 1%). In summary, PMN adhesion to IL-1-activated HEC involves both CD11/CD18-dependent mechanisms and an ELAM-1-dependent mechanism, and the relative contribution of these varies at different times of IL-1-induced HEC activation. The additive blocking observed at 4 h with mAb H18/7 in combination with CD11/CD18-directed Mab implies that members of the CD11/CD18 complex do not function as an obligate ligand(s) for ELAM-1.