THROMBOTIC THROMBOCYTOPENIC PURPURA AND SPORADIC HEMOLYTIC-UREMIC SYNDROME PLASMAS INDUCE APOPTOSIS IN RESTRICTED LINEAGES OF HUMAN MICROVASCULAR ENDOTHELIAL-CELLS

Thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremi c syndrome (HUS) are thrombotic microangiopathies that occur in the ab sence of an inflammatory response. Ultrastructural features of tissues involved in TTP/sporadic HUS suggest an apoptotic process. Consistent with these findings, we observed that TTP plasmas induce apoptosis in primary human endothelial cells (EC) of dermal microvascular but not umbilical vein origin (Laurence et al, Blood 87:3245, 1996). We now do cument the ability of plasmas from both TTP and sporadic HUS patients, but not from a patient with childhood/diarrhea-associated HUS, to ind uce apoptosis and expression of the apoptosis-associated molecule Fas (CD95) in restricted lineages of microvascular EC. EC of small vessel dermal, renal, and cerebral origin were susceptible to induction of Fa s and an apoptotic cell death. In contrast, microvascular EC of pulmon ary and hepatic origin, as well as EC of a large vessel, coronary arte ry, were resistant to both processes. This dichotomy parallels the in vivo pathology of TTP/sporadic HUS, with notable sparing of the pulmon ary and hepatic microvasculature. Apoptotic EC also had some features of a procoagulant phenotype, including depressed production of prostag landin 12 (prostacyclin). These phenomena support the pathophysiologic significance of microvascular EC apoptosis in TTP, extend it to a rel ated disorder (sporadic HUS), and suggest consideration of apoptosis i nhibitors in the experimental therapeutics of these syndromes. (C) 199 7 by The American Society of Hematology.