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Plasma from patients with idiopathic and human immunodeficiency virus-
associated thrombotic thrombocytopenic purpura induces apoptosis in
microvascular endothelial cells
J Laurence, D Mitra, M Steiner, L Staiano-Coico and E Jaffe
Laboratory for AIDS Virus Research,Department of Medicine, Cornell
University Medical College, New York 10021, USA.
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 plasma depleted of cryoprecipitate, and
low concentrations (< or = 0.1 micromol/L) of aurintricarboxylic acid
were capable of suppressing TPP plasma-mediated EC apoptosis. In
conclusion, microvascular EC apoptosis may be of pathophysiological
importance in TTP may be susceptible to interruption by blockade of
initiating signals for, or final common enzyme pathways leading to,
programmed cell death.
Volume 87,
Issue 8,
pp. 3245-3254,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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