Adhesion Molecules Mediating Recruitment of Monocytes to Inflamed Tissue

Abstract

Three families of cell-surface proteins are largely responsible for the adherence of leukocytes to cells and matrices: integrins, immunoglobulin (Ig)-related molecules and selectins. Blood monocytes express β1 integrins VLA-4, -5 and -6 and β2 integrins CDlla/CD18, CDllb/CD18 and CDllc/CD18. These cells also express the Ig-related molecules ICAM-l, -2 and -3, ligands for the β2 integrins. In addition, monocytes express L-selectin and the oligosaccharides Lex and sialyl Lex, ligands for the endothelial selectins E- and P-. In vitro studies with blocking antibodies have identified adhesion molecules participating in the adherence of monocytes to one another, to T lymphocytes and to vascular endothelial cells. These antibodies also block adhesion-dependent monocyte activities, such as cytotoxicity of tumor cells, antigen presentation, phagocytosis of large particles, induction of cytokine secretion, formation of multinucleated giant cells and HIV-induced syncytium formation. In vivo studies in animals have demonstrated participation of L-selectin and CDllb/CD18 in monocyte accumulation in inflamed peritoneum. Moreover, treatment with anti-CDll b antibodies potentiates primary listeriosis and inhibits the macrophage recruitment and granuloma formation, and anti-CD18 antibodies block ear swelling in Mycobacterium tuberculosis-immunized animals following challenge with PPD. Adhesion molecules may also play key roles in the pathogenesis of tuberculosis and AIDS.