EFFECT OF A MONOCLONAL-ANTIBODY TO VLA-4 ON LYMPHOCYTE ADHERENCE TO MICROVASCULAR AND AORTIC ENDOTHELIAL-CELLS

Lymphocyte migration out of the blood to inflammatory sites is preceded by the adherence of lymphocytes to the vascular endothelium. This lymphocyte binding is enhanced by cytokine activation of the endothelial cells (EC). Small peritoneal exudate lymphocytes (sPEL) migrate preferentially into cutaneous inflammation and to skin injected with INFγ, TNFα or LPS. These cells adhere also to rat microvascular EC and this adherence correlates well with migratory properties of sPEL. Lymphocyte EC adhesion is in part mediated by the VLA-4 molecule on the lymphocytes. Since differences between microvascular and large vessel EC have been described, we investigated whether sPEL adherence to both types of EC is governed by similar molecular mechanisms. Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INFγ, TNFα and LPS. In contrast, lymphocyte adhesion to unstimulated large vessel (aortic) EC was higher than to microvascular EC and could not be increased by cytokine or LPS treatment. Anti VLA-4 mAb inhibited the enhanced cytokine stimulated adhesion to microvascular EC without affecting adhesion of sPEL to unstimulated EC. Anti VLA-4 mAb inhibited the high spontaneous adhesion to aortic EC, suggesting that with both EC, adhesion is in part VLA-4 dependent. © 1993 Academic Press Limited.