Fuchs H, Simon M M, Wallich R, Bechtel M, Kramer M D
Institute for Immunology, Laboratory for Immunopathology, University of Heidelberg, Germany.
Infect Immun. 1996 Oct;64(10):4307-12. doi: 10.1128/iai.64.10.4307-4312.1996.
Borrelia burgdorferi is transmitted by infected ticks and causes Lyme disease. To infect distant organ sites, B. burgdorferi spirochetes must disseminate from the site of the tick bite. During dissemination from the dermal tissue, they breach tissue barriers, probably by proteolysis. The previous findings that spirochetes bind serum-derived plasminogen and that plasmin favors spirochetal invasiveness and infectivity suggested a role for plasmin in the pathogenicity of B. burgdorferi. Binding of plasminogen to spirochetes and activation into plasmin is favored in a microenvironment that is rich in plasminogen and plasminogen activators. Plasminogen is abundant in plasma and interstitial fluids, and it is increased in inflammatory exudates. Since B. burgdorferi does not express endogenous plasminogen activators, the conversion of spirochete-bound plasminogen depends on host-derived plasminogen activators. In this report, we show that both intact B. burgdorferi organisms and its recombinant outer surface lipoprotein A induce human monocytes to express and secrete urokinase-type plasminogen activator in its zymogen form (pro-uPA). Moreover, we demonstrate that the presence of B. burgdorferi accelerates the interaction between (pro-)uPA and plasmin(ogen), leading to spirochete-bound plasmin. In a pro-uPA-serum mixture, spirochete-bound plasmin activity is generated. Taken together, the data suggest that B. burgdorferi may induce pro-uPA in a monocyte-containing inflammatory site and that the spirochetal surface provides an appropriate milieu for subsequent interactions between (pro-)uPA and plasmin(ogen), which result in spirochete-bound plasmin even in the presence of inhibitors for plasminogen activators and plasmin.
伯氏疏螺旋体通过受感染的蜱传播并引起莱姆病。为了感染远处的器官部位，伯氏疏螺旋体螺旋体必须从蜱叮咬部位扩散。在从皮肤组织扩散过程中，它们可能通过蛋白水解作用突破组织屏障。先前的研究发现螺旋体结合血清来源的纤溶酶原，且纤溶酶有利于螺旋体的侵袭性和感染性，这表明纤溶酶在伯氏疏螺旋体的致病性中起作用。在富含纤溶酶原和纤溶酶原激活剂的微环境中，纤溶酶原与螺旋体的结合及激活为纤溶酶更有利。纤溶酶原在血浆和组织间液中含量丰富，在炎性渗出物中含量增加。由于伯氏疏螺旋体不表达内源性纤溶酶原激活剂，螺旋体结合的纤溶酶原的转化依赖于宿主来源的纤溶酶原激活剂。在本报告中，我们表明完整的伯氏疏螺旋体生物体及其重组外表面脂蛋白A均可诱导人单核细胞以酶原形式（pro-uPA）表达和分泌尿激酶型纤溶酶原激活剂。此外，我们证明伯氏疏螺旋体的存在加速了（pro-）uPA与纤溶酶（原）之间的相互作用，导致螺旋体结合的纤溶酶形成。在pro-uPA-血清混合物中，可产生螺旋体结合的纤溶酶活性。综上所述，数据表明伯氏疏螺旋体可能在含有单核细胞的炎症部位诱导pro-uPA，并且螺旋体表面为（pro-）uPA与纤溶酶（原）之间的后续相互作用提供了合适的环境，即使在存在纤溶酶原激活剂和纤溶酶抑制剂的情况下也会导致螺旋体结合的纤溶酶形成。
