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 establishment of infection. B. burgdorferi have previously been shown to bind to a variety of mammalian cells in vitro. Here we demonstrate that binding of B. burgdorferi to human platelets is mediated by the integrin alpha IIb beta 3 (glycoprotein IIb-IIIa), a critical receptor in thrombosis and hemostasis. Functional expression of this receptor requires platelet activation, and binding of the spirochete was observed only to activated platelets. Binding was inhibited by a synthetic Arg-Gly-Asp peptide that blocks ligand interaction with many integrins and by a synthetic peptide based on the gamma chain of fibrinogen that blocks binding to alpha IIb beta 3. In addition, attachment of the spirochete to platelets was inhibited by monoclonal antibodies directed against alpha IIb beta 3 that are known to block ligand-receptor interaction. No inhibition was seen with control peptides or with antibodies directed against other platelet receptors. B. burgdorferi bound efficiently to purified alpha IIb beta 3 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 strain did not bind to platelets. Binding to integrins may be important for the ability of B. burgdorferi to establish infection in the diverse tissues affected by Lyme disease.
Division of Rheumatology and Immunology, Tufts-New England Medical Center, Boston, MA 02111.
J
J
Coburn
J M
JM
Leong
J K
JK
Erban
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001422:Bacterial Adhesion; D001667:Binding, Competitive; D001792:Blood Platelets / Q000382:microbiology*; D015748:Borrelia burgdorferi Group / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D008193:Lyme Disease / Q000097:blood / Q000382:microbiology*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016023:Integrins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C047981:arginyl-glycyl-aspartic acid