INTEGRIN ALPHA-IIB-BETA-3 MEDIATES BINDING OF THE LYME-DISEASE AGENT BORRELIA-BURGDORFERI TO HUMAN PLATELETS

Lyme disease is a chronic, multisystemic infection caused by the tick- borne spirochete Borrelia burgdorferi. Attachment of the spirochete to host cells via specific receptors is likely to be important in the es tablishment of infection. B. burgdorferi have previously been shown to bind to a variety of mammalian cells in vitro. Here we demonstrate th at binding of B. burgdorferi to human platelets is mediated by the int egrin alpha(IIb)beta3 (glycoprotein IIb-IIIa), a critical receptor in thrombosis and hemostasis. Functional expression of this receptor requ ires platelet activation, and binding of the spirochete was observed o nly to activated platelets. Binding was inhibited by a synthetic Arg-G ly-Asp peptide that blocks ligand interaction with many integrins and by a synthetic peptide based on the gamma chain of fibrinogen that blo cks binding to alpha(IIb)beta3. In addition, attachment of the spiroch ete to platelets was inhibited by monoclonal antibodies directed again st alpha(IIb)beta3 that are known to block ligand-receptor interaction . No inhibition was seen with control peptides or with antibodies dire cted against other platelet receptors. B. burgdorferi bound efficientl y to purified alpha(IIb)beta3 but did not bind to platelets deficient in this integrin. Efficient platelet binding was displayed by a cloned , infectious B. burgdorferi strain, whereas a cloned noninfectious str ain did not bind to platelets. Binding to integrins may be important f or the ability of B. burgdorferi to establish infection in the diverse tissues affected by Lyme disease.