Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation.
It has been suggested that endothelial apoptosis is a primary lesion in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). We tested this hypothesis by examining the phenotypic signatures of endothelial microparticles (EMP) in TTP patients. In addition, the effect of TTP plasma on microvascular endothelial cells (MVEC) in culture was further delineated. EMP released by endothelial cells (EC) express markers of the parent EC; EMP released in activation carry predominantly CD54 and CD62E, while those in apoptosis CD31 and CD105. We investigated EMP release in vitro and in TTP patients. Following incubation of MVEC with TTP plasma, EMP and EC were analysed by flow cytometry for the expression of CD31, CD51, CD54, CD62E, CD105, CD106 and von Willebrand factor (VWF) antigen. EMP were also analysed in 12 TTP patients. In both EC and EMP, CD62E and CD54 expression were increased 3- to 10-fold and 8- to 10-fold respectively. However, CD31 and CD105 were reduced 40-60% in EC but increased twofold in EMP. VWF expression was found in 55 +/- 15% of CD62E+ EMP. Markers of apoptosis were negative. In TTP patients, CD62E+ and CD31+/CD42b- EMP were markedly elevated, and preceded and correlated well with a rise in platelet counts and a fall in lactate dehydrogenase. CD62E+ EMP (60 +/- 20%) co-expressed VWF and CD62E. The ratio of CD31+/42b- to CD62E+ EMP exhibited a pattern consistent with activation. In conclusion, our studies indicate endothelial activation in TTP. EMP that co-express VWF and CD62E could play a role in the pathogenesis of TTP.
Jimenez
Joaquin J
JJ
Wallace H Coulter Platelet Laboratory, Division of Hematology/Oncology, University of Miami School of Medicine, Miami, FL 33136, USA. jjimenez@med.miami.edu
Jy
Wenche
W
Mauro
Lucia M
LM
Horstman
Lawrence L
LL
Soderland
Carl
C
Ahn
Yeon S
YS
D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002478:Cells, Cultured; D019040:E-Selectin / Q000032:analysis; D042783:Endothelial Cells / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000032:analysis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018709:Statistics, Nonparametric; D014841:von Willebrand Factor / Q000032:analysis*
D015415:Biomarkers; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor