Koethe S M, Nelson K E, Becker C G
Department of Pathology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Immunol. 1995 Jul 15;155(2):826-35.
Tobacco glycoprotein (TGP), a polyphenol-rich glycoprotein isolated from tobacco leaves, activates the classical complement pathway through a mechanism that appears to involve direct interaction with C1q. A binding site on C1q for TGP can be localized by competitive inhibition with DNA to a region located in the junction between the collagen-like and globular regions of the molecule. A protein with activity similar to TGP has also been isolated from cigarette smoke condensate (TGP-S); it shares a binding site on C1q with TGP and has similar functional activity, with the exception that complement activation does not proceed to formation of a C3 cleaving enzyme. The ability of TGP and TGP-S to activate complement can be partially duplicated using polyphenols associated with tobacco leaf and smoke, i.e., chlorogenic acid and rutin. These polyphenols also compete with TGP for a binding site on immobilized C1q, suggesting that the polyphenol portion of TGP is critical for activation of complement. These results provide an additional mechanism for complement activation by cigarette products that, in vivo, could result in a localized complement depletion, generation of biologically active complement cleavage products, and initiation of an inflammatory response.
烟草糖蛋白（TGP）是一种从烟草叶片中分离出来的富含多酚的糖蛋白，它通过一种似乎涉及与C1q直接相互作用的机制激活经典补体途径。TGP在C1q上的结合位点可通过与DNA的竞争性抑制定位到分子中胶原样区域和球状区域之间连接处的一个区域。一种与TGP活性相似的蛋白质也已从香烟烟雾冷凝物中分离出来（TGP-S）；它与TGP在C1q上共享一个结合位点，并且具有相似的功能活性，不同之处在于补体激活不会进行到形成C3裂解酶。使用与烟草叶片和烟雾相关的多酚，即绿原酸和芦丁，可以部分重现TGP和TGP-S激活补体的能力。这些多酚也与TGP竞争固定化C1q上的结合位点，这表明TGP的多酚部分对于补体激活至关重要。这些结果为香烟产品激活补体提供了另一种机制，在体内，这可能导致局部补体消耗、生物活性补体裂解产物的产生以及炎症反应的启动。
