title: Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes.
abstract: The comparative roles of the endothelial cell (EC) adhesion receptors VCAM-1 and ICAM-1 during the adhesion and transendothelial migration of T cells were examined. The adhesion of T cells to IL-1-activated EC was markedly, but not completely, inhibited by mAb to VCAM-1 as well as to its counter-receptor, VLA-4, whereas, T cell binding to IL-1-activated EC was not blocked by mAb to ICAM-1 or to its counter-receptor, LFA-1. In contrast, LFA-1/ICAM-1, but not VLA-4/VCAM-1, mediated much, but not all, of the binding of T cells to unstimulated EC. Activation of T cells with phorbol dibutyrate and ionomycin alter the receptor-counter-receptor pairs used for binding to EC. Regardless of the activation status of the EC, the binding of activated T cells was not blocked by mAb to VLA-4 or VCAM-1. Moreover, the binding of activated T cells to EC was blocked to a lesser degree by mAb to LFA-1 than that of resting T cells, and mAb to ICAM-1 blocked binding only modestly. The role of VCAM-1 and ICAM-1 during the transendothelial migration of T cells was also examined. Regardless of the activation status of the T cells or the EC, VCAM-1 was never found to function during transendothelial migration, even when it mediated the binding of resting T cells to IL-1-activated EC. In contrast, ICAM-1 played an important role in transendothelial migration under all of the conditions examined, including situations when T cell-EC binding was not mediated by ICAM-1. Immunoelectron microscopic analysis of transendothelial migration supported the conclusion that ICAM-1 but not VCAM-1 played a central role in this process. Thus, ICAM-1 was prominently and uniformly expressed at all EC membrane sites that were in contact with bound and migrating T cells, whereas VCAM-1 was localized to the luminal surface of IL-1-activated EC, but was often absent from the surface of the EC in contact with T cells undergoing transendothelial migration. These studies confirm that ICAM-1 and VCAM-1 play reciprocal roles in the binding of resting T cells to resting and IL-1-activated EC, respectively, but a less prominent role in the binding of activated T cells. Moreover, ICAM-1 but not VCAM-1 plays a role in transendothelial migration, regardless of the receptor-counter-receptor pairs used for initial binding.
authors.affiliation: Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern, Medical Center, Dallas 75235.
authors.forename: N
authors.initials: N
authors.lastname: Oppenheimer-Marks
authors.forename: L S
authors.initials: LS
authors.lastname: Davis
authors.forename: D T
authors.initials: DT
authors.lastname: Bogue
authors.forename: J
authors.initials: J
authors.lastname: Ramberg
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008854:Microscopy, Electron; D016029:Receptors, Very Late Antigen / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1