ENDOTHELIAL-LEUKOCYTE ADHESION MOLECULE-1-DEPENDENT AND LEUKOCYTE (CD11/CD18)-DEPENDENT MECHANISMS CONTRIBUTE TO POLYMORPHONUCLEAR LEUKOCYTE ADHESION TO CYTOKINE-ACTIVATED HUMAN VASCULAR ENDOTHELIUM

  • 1 April 1989
    • journal article
    • research article
    • Vol. 142  (7) , 2257-2263
Abstract
We have examined the contributions of endothelial-leukocyte adhesion molecule-1 (ELAM-1) and the complex of leukocyte surface adehsion 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 H18/7), 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 or 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.

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