INTEGRIN CR3 MEDIATES THE BINDING OF NONSPECIFICALLY OPSONIZED BORRELIA-BURGDORFERI TO HUMAN PHAGOCYTES AND MAMMALIAN-CELLS

Like other pathogens, the spirochete Borrelia burgdorferi, the agent o f Lyme disease, possesses multiple pathways for cell binding; adhesion to phagocytic cells is of particular interest since it reportedly occ urs even in the absence of specific antibodies. This study sets out to investigate how B. burgdorferi binds to human polymorphonuclear leuko cytes (PMNs) when an exogenous complement is added and how the CR3 com plement receptor, known as Mac-1 or alpha(m) beta(2) integrin, is invo lved in the binding process. Experiments performed on PMNs and CHO Mac -1-expressing cells demonstrate that binding is inhibited by monoclona l anti-iC3b site antibodies, fibrinogen, and N-acetyl-D-glucosamine. T hese findings, which are not present with non-Mac-transfected CHO cell s, indicate that the integrin alpha(m) beta(2) acts as a receptor for spirochetes in nonimmune phagocytosis; furthermore, binding occurs on different domains of the CD11b subunit, involving the iC3b site and th e lectin domain. The interaction of B. burgdorferi with alpha(m) beta( 2) integrin adds a novel pathway to Borrelia-phagocyte binding; not on ly does this binding affect the early stages of phagocytosis, but also it can influence the effector intracellular mechanisms which are acti vated by the beta(2) integrin, as are the cytotoxic mechanisms.