Herzberg M C
Department of Preventive Sciences, School of Dentistry, University of Minnesota, Minneopolis 55455, USA.
Crit Rev Oral Biol Med. 1996;7(3):222-36. doi: 10.1177/10454411960070030201.
Infective endocarditis is characterized by the formation of septic masses of platelets on the surfaces of heart valves and is most commonly caused by viridans streptococci. Streptococcal virulence in endocarditis involves factors that promote infectivity and pathogenicity. Adhesins and exopolysaccharide (glycocalyx) contribute to infectivity. Although many factors may contribute to pathogenicity, the platelet aggregation-associated protein (PAAP) of Streptococcus sanguis contributes directly to the development of experimental endocarditis. PAAP is synthesized as a rhamnose-rich glycoprotein of 115 kDa and contains a collagen-like platelet-interactive domain, pro-gly-glu-gln-gly-pro-lys. Expressed on the cell wall of platelet aggregation-inducing strains (Agg+) of S. sanguis, PAAP apparently interacts with a signal-transducing receptor complex on platelets, which includes a novel 175-kDa alpha 2-integrin-associated protein and a 65-kDa collagen-binding component. From available data, the role of PAAP in the pathogenesis of experimental endocarditis may be explained by a proposed mechanistic model. On injured heart valves, PAAP first enhances platelet accumulation into a fibrin-enmeshed thrombus (vegetation), within which S. sanguis colonizes. Colonizing bacteria must resist platelet microbicidal protein (PMPR). The aggregation of platelets on the heart valve may be potentiated by an ectoATPase expressed on the surface of the S. sanguis and platelet alpha-adrenoreceptors that respond to endogenous catecholamines. The expression of PAAP may be modified during infection. Collagen is exposed on damaged heart valves; fever (heat shock) occurs during endocarditis. In response to heat shock or collagen in vitro, PAAP expression is altered. After colonization, streptococcal exotoxin(s) may cause fever. Proteases and other enzymes from streptococci and host sources may directly destroy the heart valves. When PAAP is unexpressed or neutralized with specific antibodies, experimental endocarditis runs a milder course and vegetations are smaller. The data suggest strongly, therefore, that the role of PAAP may overlap the colonization function of putative adhesins such as FimA or SsaB. Finally, PAAP also contributes to the development of the characteristic septic mural thrombus (vegetation) of infective endocarditis and the signs of valvular pathology.
感染性心内膜炎的特征是在心脏瓣膜表面形成血小板败血团块，最常见的病因是草绿色链球菌。心内膜炎中的链球菌毒力涉及促进感染性和致病性的因素。黏附素和胞外多糖（糖萼）有助于感染性。虽然许多因素可能导致致病性，但血链球菌的血小板聚集相关蛋白（PAAP）直接促成实验性心内膜炎的发展。PAAP作为一种富含鼠李糖的115 kDa糖蛋白合成，含有一个胶原样血小板相互作用结构域，即脯氨酸-甘氨酸-谷氨酸-谷氨酰胺-甘氨酸-脯氨酸-赖氨酸。PAAP表达于血链球菌血小板聚集诱导菌株（Agg+）的细胞壁上，显然与血小板上的信号转导受体复合物相互作用，该复合物包括一种新的175 kDaα2整合素相关蛋白和一种65 kDa胶原结合成分。根据现有数据，PAAP在实验性心内膜炎发病机制中的作用可用一个提出的机制模型来解释。在受损的心脏瓣膜上，PAAP首先增强血小板聚集形成纤维蛋白包绕的血栓（赘生物），血链球菌在其中定植。定植的细菌必须抵抗血小板杀菌蛋白（PMPR）。血链球菌表面表达的一种胞外ATP酶和对内源性儿茶酚胺有反应的血小板α-肾上腺素能受体可能会增强血小板在心脏瓣膜上的聚集。PAAP的表达在感染过程中可能会发生改变。胶原暴露在受损的心脏瓣膜上；心内膜炎期间会出现发热（热休克）。在体外，对热休克或胶原的反应会改变PAAP的表达。定植后，链球菌外毒素可能会引起发热。链球菌和宿主来源的蛋白酶及其他酶可能会直接破坏心脏瓣膜。当PAAP不表达或用特异性抗体中和时，实验性心内膜炎的病程会较轻，赘生物也较小。因此，数据强烈表明，PAAP的作用可能与假定的黏附素如FimA或SsaB的定植功能重叠。最后，PAAP也有助于感染性心内膜炎特征性败血性壁血栓（赘生物）的形成以及瓣膜病变的体征。
