Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue.

Abstract

SummaryTo determine the role of vascular cell adhesion molecule 1 (VCAM-1) /very late activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing antigen-induced eosinophil and T cell recruitment into the tissue, we studied the effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on the eosinophil and T cell infiltration of the trachea induced by antigen inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but did not affect blood eosinophil counts without antigen challenge in sensitized mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced on the endothelium of the trachea after antigen challenge. In addition, pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression only by 27% and had no significant effect on antigen-induced eosinophil infiltration into the trachea. The in vivo blocking of VCAM-1 and VLA-4 inhibited antigen-induced CD4 + and CD8 + T cell infiltration into the trachea more potently than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the in vivo blocking of LFA-1, but not of ICAM-1, increased blood lymphocyte counts more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4 interaction plays a predominant role in controlling antigen-induced eosinophil and T cell recruitment into the tissue and that the induction of VCAM-1 expression on the endothelium at the site of allergic inflammation regulates this eosinophil and T cell recruitment.

Allergen‐induced inflammation and airway epithelial and smooth muscle cell proliferation: role of Jun N‐terminal kinase

“…TNFa activation of ICAM-1 expression is also associated with JNK activation (De Cesaris et al, 1999). Other adhesion molecules such as a 4 -integrin and VCAM-1 may also be regulated by JNK and these may have important roles in the recruitment of T cells and eosinophils during allergen-induced airway inflammation (Nakajima et al, 1994).…”

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

“…These data corroborate our findings that CCL25 induced the transmigration of γδ T lymphocytes through endothelial cells, via the interaction of α 4 β 7 integrin to MadCAM-1/VCAM-1. During allergy, the expression of VCAM-1 (but not ICAM-1) by mouse endothelium has been shown to be upregulated [40]. In addition, the in vitro stimulation of HUVECs by the Th2 cytokine IL-4 also induced the expression of VCAM-1, failing to alter ICAM-1 expression [41], which is in accordance with our observations that IL-4 triggered increased expression of VCAM-1 and MadCAM-1 on mouse endothelial cells, but not of ICAM-1 (not shown).…”

Role of α4 integrin and its ligand VCAM‐1 in the specific extravasation of a tumor‐specific TH2 clone into tumor tissue that initiates its rejection

“…6,9,[37][38][39] Several investigators have reported that T-cell migration from blood vessels into the extravascular matrix involves adhesion between integrin ␣4␤1 molecules on T cells and VCAM-1 molecules on vascular endothelial cells. 29,40,41 Moreover, in vitro adhesion of integrin ␣4␤1 on human T cells to VCAM-1 can be nonspecifically upregulated by a chemokine, MIP-1␤. 42,43 We investigated the relationship between YS1093 cell and chemokines by in vitro studies.…”

“…1 Since it has been reported that the interaction of ␣4␤1 integrin and VCAM-1 plays an important role in the migration of T cells into peripheral tissues, 29,31 we examined whether the in vivo antitumor effect of YS1093 cells could be abrogated by preincubating YS1093 cells with anti-␣4 integrin MAb and injecting anti-VCAM-1 MAb along with the adoptive T-cell transfer. Figures 1 and 2 reveal that the blocking effects of the 2 MAbs markedly inhibited the tumor regression induced by YS1093 transfer, whereas untreated cells transferred along with an isotype control IgG continued to induce tumor regression.…”

“…26,27 For example, the interaction of integrin ␣4␤1 on lymphocytes that have not been activated by specific antigen with endothelial VCAM-1 is thought to be essential for the trafficking of these T cells into peripheral tissues. 28,29 However, the transendothelial migration mechanism that is used by antigen-specific CD4 ϩ T cells such as tumorspecific T cells remains unclear. It is critical that this process be clarified as it is likely to be an important consideration in the development of anticancer immunotherapy.…”