Enhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura.

TitleEnhanced endothelial cell apoptosis in splenic tissues of patients with thrombotic thrombocytopenic purpura.
Publication TypeJournal Article
Year of Publication1999
AuthorsDang CT, Magid MS, Weksler B, Chadburn A, Laurence J
Date Published1999 Feb 15
KeywordsAdolescent, Adult, Apoptosis, Child, Endothelium, Vascular, fas Receptor, Female, Humans, In Situ Nick-End Labeling, Male, Middle Aged, Purpura, Thrombotic Thrombocytopenic, Spleen

Idiopathic thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy of obscure etiology. The fundamental pathologic lesion is a hyaline thrombus composed of platelets and some fibrin accompanied by endothelial cell proliferation and detachment, in the absence of an inflammatory response. We have previously demonstrated that plasmas from patients with both idiopathic TTP and a related disorder, sporadic hemolytic-uremic syndrome (HUS), induce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in vitro in those lineages of microvascular endothelial cells (MVECs) that are affected pathologically. We now demonstrate the presence of enhanced MVEC apoptosis in splenic tissues from patients with TTP, documented by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) and morphology. This is accompanied by elevated Fas expression. It contrasts with the absence of apoptosis in splenic tissues obtained after splenectomy for trauma or immune thrombocytopenic purpura. TUNEL-positive cells, identified by immunohistochemistry as MVECs or macrophages, presumably engulfing apoptotic ECs, are noted in numerous areas, including those apart from microthrombi. Thus, it is unlikely that EC apoptosis is simply a sequela of thrombus formation. Based on these data, we propose that MVEC apoptosis is of pathophysiologic significance in idiopathic TTP/sporadic HUS.

Alternate JournalBlood
PubMed ID9949169
Grant ListAI41327 / AI / NIAID NIH HHS / United States
DE11348 / DE / NIDCR NIH HHS / United States
HL55646 / HL / NHLBI NIH HHS / United States
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