Nardi M, Tomlinson S, Greco M A, Karpatkin S
Department of Pediatrics, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Cell. 2001 Sep 7;106(5):551-61. doi: 10.1016/s0092-8674(01)00477-9.
Immunologic thrombocytopenia is seen commonly in HIV-1 infection. The pathogenesis of this problem has been unclear, but it is associated with circulating immune complexes that contain platelet membrane components and anti-platelet membrane GPIIIa49-66 IgG antibodies. These antibodies cause acute thrombocytopenia when injected into mice. We now show that purified anti-GPIIIa49-66 causes platelet fragmentation, in vitro in the absence of complement, and in vivo in wild-type and C3-deficient mice. The mechanism of complement-independent platelet lysis is shown to be caused by the antibody-induced generation of H202, as indicated by in vitro experiments with inhibitors of reactive oxygen species, and in vivo studies carried out with p47phox-deficient mice. Thus, a novel mechanism of immunologic platelet clearance is described in which an anti-platelet IgG causes platelet fragmentation via the induction of reactive oxygen species.
免疫性血小板减少症在HIV-1感染中很常见。这个问题的发病机制尚不清楚，但它与含有血小板膜成分和抗血小板膜GPIIIa49-66 IgG抗体的循环免疫复合物有关。将这些抗体注射到小鼠体内会导致急性血小板减少症。我们现在表明，纯化的抗GPIIIa49-66在体外无补体的情况下以及在野生型和C3缺陷型小鼠体内都会导致血小板碎片化。如使用活性氧抑制剂的体外实验以及对p47phox缺陷型小鼠进行的体内研究所表明的，不依赖补体的血小板溶解机制显示是由抗体诱导产生的H2O2引起的。因此，描述了一种新的免疫性血小板清除机制，其中抗血小板IgG通过诱导活性氧导致血小板碎片化。
