生物谷报道:法国研究人员9日在blood发表论文,阐述了与血友病A相关的VIII因子相互作用影响其免疫周期。
VIII因子(FVIII)作为凝血因子,一种是在生理条件下自身产生的,一种是作为血友病A的治疗药物而外源性输入的。FVIII与多种糖蛋白相互作用,参与局部止血。无论是内源性的,还是外源性的FVIII,最后都由免疫系统或清除细胞排除。这取决于多种因素,如个体免疫情况、不同时间、不同部位、FVIII和相互作用因子含量、亲和性等。
研究者描述了FVIII生命周期中建立的不同相互作用,特别是参与了先天性或后天性免疫应答作用,认为这有助于理解FVIII动力学,有助于理解长效止血药物无医源性免疫原性。(生物谷www.bioon.com)
生物谷推荐原始出处:
Blood. 2008 May 9; : 18469198 (P,S,E,B,D)
Dynamics of factor VIII interactions determine its immunological fate in hemophilia A.
Sebastien Lacroix-Desmazes, Ana-Maria Navarrete, Sebastien Andre, Jagadeesh Bayry, Srinivas V Kaveri, Suryasarathi Dasgupta
INSERM UMR S 872, Universite Pierre et Marie Curie, Paris, France.
Pro-coagulant factor VIII (FVIII) is either produced endogenously under physiological conditions, or administered exogenously as a therapeutic hemostatic drug in patients with hemophilia A. In the circulation, FVIII interacts with a multitude of glycoproteins, and may be used for coagulation at the sites of bleeding, eliminated by scavenger cells or be processed by the immune system, either as a self-constituent or as a foreign antigen. The fate of FVIII is dictated by the immune status of the individual, the location of FVIII in the body at a given time-point, and the inflammatory microenvironment. It also depends on the local concentration of FVIII and of each interacting partner, and on the affinity of the respective interactions. FVIII, by virtue of its promiscuity, thus constitutes the core of a dynamic network that links the coagulation cascade, cells of the immune system and, presumably, the inflammatory compartment. We describe the different interactions that FVIII is prone to establish during its life cycle, with a special focus on players of the innate and adaptive immune response. Lessons can be learned from understanding the dynamics of FVIII interactions; lessons that should pave the way to the conception of long-lasting hemostatic drugs devoid of iatrogenic immunogenicity.