INTEGRIN ALPHA-IIB-BETA-3 MEDIATES BINDING OF THE LYME-DISEASE AGENT BORRELIA-BURGDORFERI TO HUMAN PLATELETS
INTEGRIN ALPHA-IIB-BETA-3 MEDIATES BINDING OF THE LYME-DISEASE AGENT BORRELIA-BURGDORFERI TO HUMAN PLATELETS
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DOI：
10.1073/pnas.90.15.7059
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发表时间：
1993-08-01
影响因子：
11.1
通讯作者：
ERBAN, JK
中科院分区：
文献类型：
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作者：
COBURN, J;LEONG, JM;ERBAN, JK
莱姆病是一种由蜱传播的伯氏疏螺旋体引起的慢性多系统感染。螺旋体通过特定受体附着到宿主细胞上可能是建立感染的重要途径。伯氏疏螺旋体先前已被证明能在体外与多种哺乳动物细胞结合。在这里，我们证明了伯氏疏螺旋体与人血小板的结合是由整合素α (IIb) β 3（糖蛋白IIb- iiia）介导的，这是一种血栓和止血的关键受体。该受体的功能表达需要活化血小板，并且仅观察到螺旋体与活化血小板的结合。合成的Arg-Gly-Asp肽阻断配体与许多整合素的相互作用，合成的基于纤维蛋白原γ链的肽阻断与α (IIb) β a3的结合。此外，针对α (IIb) β 3的单克隆抗体抑制了螺旋体与血小板的附着，已知α (IIb) β 3可阻断配体与受体的相互作用。对照肽或针对其他血小板受体的抗体未见抑制作用。伯氏疏螺旋体能有效地与纯化的α (IIb) β 3结合，但不能与缺乏这种整合素的血小板结合。克隆的传染性伯氏疏螺旋体菌株显示出有效的血小板结合，而克隆的非传染性伯氏疏螺旋体菌株不与血小板结合。与整合素的结合可能对伯氏疏螺旋体在莱姆病影响的各种组织中建立感染的能力很重要。
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)beta3 (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)beta3. In addition, attachment of the spirochete to platelets was inhibited by monoclonal antibodies directed against alpha(IIb)beta3 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)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 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.