PMID: 8605340Apr 15, 1996Paper

Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells.

Blood
J LaurenceE Jaffe

Abstract

The pathogenesis of thrombotic thrombocytopenic purpura (TTP) is obscure. It is manifested classically by platelet thrombi and localized microvascular endothelial cell (EC) proliferation, in the absence of an inflammatory response. It is statistically associated with human retroviral disease, but pathological studies of TTP lesions have been unable to establish whether perturbation of the endothelium is a primary or secondary event, irrespective of the presence of retroviral infection. We document that plasma from all of four acute TTP patients, with or without human immunodeficiency virus infection, can induce apoptosis in cultured ECs of microvascular but not large vessel origin. This process was documented by three different methods, (1) laser-illuminated light scatter, (2) quantitation of the pre-G1 Ao peak on DNA histograms and direct visualization of chromatin fragmentation by acridine orange and 4'6-diamidino-2-phenylindole staining, and (3) agarose gel electrophoresis of low molecular weight cellular DNA. Apoptosis was independent of tumor necrosis factor-alpha secretion or the presence of CD36 on microvascular ECs but was linked to the rapid induction of Fas (CD95) on these cells. Soluble anti-Fas antibody, normal plas...Continue Reading

Citations

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis