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.

IL‐21 promoting angiogenesis contributes to the development of psoriasis

“…It is expressed by EC, epithelial cells, and immune cells 22 . The main function of ICAM‐1 was verified as regulating leukocyte recruitment from circulation to sites of inflammation 23,24 . As well, ICAM‐1 was found to induce angiogenesis, support the survival of microvessels, 25 and stimulate EC proliferation and migration 26,27 .…”

“…22 The main function of ICAM-1 was verified as regulating leukocyte recruitment from circulation to sites of inflammation. 23,24 As well, ICAM-1 was found to induce angiogenesis, support the survival of microvessels, 25 and stimulate EC proliferation and migration. 26,27 Activated EC release the soluble vascular cell adhesion molecule-1 and ICAM-1, which could be regarded as markers of endothelial activation.…”

Annotation of CD8+ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy

“…ICAM-1 functions in multiple steps of the cancer immune cycle, and its expression on DCs collaborates with the surface receptor LFA-1 on T cells to facilitate antigen presentation 37 . Meanwhile, ICAM-1 expressed in endothelial cells interacts with LFA-1 to promote the trafficking and infiltration of activated effector T cells into tumors 38 , 39 . Our research suggests a new function of ICAM-1 in CD8 + T cells in the TME.…”