Cinco M, Murgia R, Presani G, Perticarari S
Dipartimento di Scienze Biomediche, Università di Trieste, Italy.
Infect Immun. 1997 Nov;65(11):4784-9. doi: 10.1128/iai.65.11.4784-4789.1997.
Like other pathogens, the spirochete Borrelia burgdorferi, the agent of Lyme disease, possesses multiple pathways for cell binding; adhesion to phagocytic cells is of particular interest since it reportedly occurs even in the absence of specific antibodies. This study sets out to investigate how B. burgdorferi binds to human polymorphonuclear leukocytes (PMNs) when an exogenous complement is added and how the CR3 complement receptor, known as Mac-1 or alpha(m)beta2 integrin, is involved in the binding process. Experiments performed on PMNs and CHO Mac-1-expressing cells demonstrate that binding is inhibited by monoclonal anti-iC3b site antibodies, fibrinogen, and N-acetyl-D-glucosamine. These findings, which are not present with non-Mac-transfected CHO cells, indicate that the integrin alpha(m)beta2 acts as a receptor for spirochetes in nonimmune phagocytosis; furthermore, binding occurs on different domains of the CD11b subunit, involving the iC3b site and the lectin domain. The interaction of B. burgdorferi with alpha(m)beta2 integrin adds a novel pathway to Borrelia-phagocyte binding; not only does this binding affect the early stages of phagocytosis, but also it can influence the effector intracellular mechanisms which are activated by the beta2 integrin, as are the cytotoxic mechanisms.
与其他病原体一样，莱姆病病原体伯氏疏螺旋体拥有多种细胞结合途径；对吞噬细胞的黏附尤其令人关注，因为据报道即使在没有特异性抗体的情况下这种黏附也会发生。本研究旨在探究添加外源性补体时伯氏疏螺旋体如何与人多形核白细胞（PMN）结合，以及被称为Mac-1或α(m)β2整合素的CR3补体受体如何参与结合过程。在PMN和表达CHO Mac-1的细胞上进行的实验表明，单克隆抗iC3b位点抗体、纤维蛋白原和N-乙酰-D-葡萄糖胺可抑制结合。这些在未转染Mac的CHO细胞中不存在的发现表明，整合素α(m)β2在非免疫吞噬作用中作为螺旋体的受体；此外，结合发生在CD11b亚基的不同结构域上，涉及iC3b位点和凝集素结构域。伯氏疏螺旋体与α(m)β2整合素的相互作用为伯氏疏螺旋体-吞噬细胞结合增添了一条新途径；这种结合不仅影响吞噬作用的早期阶段，还能影响由β2整合素激活的效应细胞内机制，细胞毒性机制也是如此。
