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Blood, 15 July 2008, Vol. 112, No. 2, pp. 218. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kwaan, H. C. Search for Related Content PubMed PubMed Citation Articles by Kwaan, H. C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS Comment on Stefanescu et al, page 340 Endothelial cells are not all alike Hau C. Kwaan NORTHWESTERN UNIVERSITY MEDICAL SCHOOL In this issue of Blood, Stefanescu et al discover the characteristics that distinguish sensitive versus nonsensitive endothelial cells to injury by TTP plasma. An important factor in the pathogenesis of thrombotic thrombocytopenic purpura (TTP) is injury to microvascular endothelial cells (MVECs). Such injury was demonstrated in earlier work by Mitra et al, who found that apoptosis of MVECs can be induced in vitro by plasma obtained from TTP patients. They further observed that MVECs derived from the brain, kidneys, and skin are most sensitive to TTP plasma, whereas those derived from lung and liver are not.1 Macrovascular endothelial cells derived from major vessels do not share this behavior. In this issue of Blood, Ste-fanescu and coauthors, part of the same research group as Mitra et al, reveal the distinguishing features of sensitive versus nonsensitive MVECs. In a series of experiments, Stefanescu and colleagues used MVECs derived from the skin as representative of the sensitive group and MVECs derived from the lung as representative of the nonsensitive group. They also studied large-vessel endothelial cells. TTPplasma–induced apoptosis in these endothelial cells was studied in the presence of tumor ne-crosis factor–related apoptosis-inducing li-gand (TRAIL) and IFN-. They clarify the mechanism of apoptosis by observing that, in the sensitive MVECs, ubiquitination of the caspase 8 regulator c-FLIP led to degradation of its proteasome. Likewise, c-FLIP silencing with anti-FLIP siRNA in the nonsensitive MVECs rendered them sensitive to apoptosis. Such differences in sensitivity in the various lineages of MVECs are consistent with the clinical manifestations of TTP, being common in the central nervous system and kidneys and rare in the lungs and liver.2 It would, perhaps, have been more exciting if the authors had shown similar findings with the other known sensitive MVECs (those derived from the brain and kidney) and with the other known nonsensitive MVECs (those derived from the liver). Nevertheless, their discovery of the role of c-FLIP in regulation of MVEC apoptosis may have important therapeutic implications for TTP. What is still an enigma is the link between endothelial injury and the development of autoantibodies against ADAMTS13. The presence of the antibodies results in a drastic lowering of blood levels of ADAMTS13, and leads to platelet aggregation and microvascular platelet thrombi formation. Such investigative challenges are not abating, but the present findings represent yet another step toward solving this riddle. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. REFERENCES Mitra D, Jaffe EA, Weksler B, Hajjar KA, Soderland C, Laurence J. Thrombotic thrombocytopenic purpura and sporadic hemolytic-uremic syndrome plasmas induce apoptosis in restricted lineages of human microvascular endothelial cells. Blood. 1997;89:1224–1234.[Abstract/Free Full Text] Kwaan HC, Boggio LN. The clinical spectrum of thrombotic thrombocytopenic purpura. Semin Thromb Hemost. 2005;31:673–680.[CrossRef][Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Synergistic interactions between interferon- and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma–associated apoptosis Radu Stefanescu, Dustin Bassett, Rozbeh Modarresi, Francisco Santiago, Mohamad Fakruddin, and Jeffrey Laurence Blood 2008 112: 340-349. [Abstract] [Full Text] [PDF] This article has been cited by other articles: M. Ghielmini and E. Zucca How I treat mantle cell lymphoma Blood, August 20, 2009; 114(8): 1469 - 1476. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kwaan, H. C. Search for Related Content PubMed PubMed Citation Articles by Kwaan, H. C. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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