Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium.
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.
Luscinskas
F W
FW
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Brock
A F
AF
Arnaout
M A
MA
Gimbrone
M A
MA
D000911:Antibodies, Monoclonal / Q000502:physiology; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004730:Endothelium, Vascular / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007375:Interleukin-1; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins