Chong B H, Fawaz I, Chesterman C N, Berndt M C
Department of Haematology, St George Hospital, Kogarah, NSW, Australia.
Br J Haematol. 1989 Oct;73(2):235-40. doi: 10.1111/j.1365-2141.1989.tb00258.x.
The interaction of the heparin-dependent antibody with heparin and platelets has been studied using the sera and purified IgG of four patients with heparin-induced thrombocytopenia. Both normal platelets and Bernard-Soulier syndrome (BSS) platelets which lack glycoprotein (GP) Ib. GPV and GPIX, aggregated in response to patient serum or IgG, but only in the presence of heparin. A monoclonal antibody (Mab) against platelet Fc II receptor (IV.3) strongly inhibited the heparin-dependent aggregation of both normal and BSS platelets induced by patient sera/IgG. Inhibition by the anti-GPIb Mab (AK2) was variable and occurred only with normal platelets. Anti-GPIX Mab (FMC 25) was not inhibitory with either normal or BSS platelets. Similar results were obtained using 14C-serotonin release instead of platelet aggregation as a measure of platelet activation. These findings suggest that (1) the reaction of the heparin-dependent antibody with platelets and heparin is mediated by a Fc-dependent mechanism, (2) GPIb, GPV and GPIX are not involved in this reaction, and (3) the inhibitory effect of anti-GPIb Mab on normal platelets is due to steric interference consistent with the platelet Fc receptor being in close proximity to GPIb.
利用4例肝素诱导的血小板减少症患者的血清和纯化的IgG,研究了肝素依赖性抗体与肝素和血小板的相互作用。正常血小板和缺乏糖蛋白(GP)Ib、GPV和GPIX的伯纳德-索利尔综合征(BSS)血小板,在患者血清或IgG作用下均会聚集,但仅在肝素存在的情况下。一种针对血小板Fc II受体(IV.3)的单克隆抗体(Mab)强烈抑制患者血清/IgG诱导的正常和BSS血小板的肝素依赖性聚集。抗GPIb单克隆抗体(AK2)的抑制作用不稳定,且仅在正常血小板中出现。抗GPIX单克隆抗体(FMC 25)对正常或BSS血小板均无抑制作用。使用14C-5-羟色胺释放而非血小板聚集作为血小板活化的指标,也得到了类似结果。这些发现表明:(1)肝素依赖性抗体与血小板和肝素的反应是由Fc依赖性机制介导的;(2)GPIb、GPV和GPIX不参与此反应;(3)抗GPIb单克隆抗体对正常血小板的抑制作用是由于空间位阻,这与血小板Fc受体与GPIb紧密相邻一致。