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Anti-endothelial cell antibodies from patients with thrombotic thrombocytopencpurpura specifically activate small vessel endothelial cellsPraprotnik, Sonja ...Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknownetiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic ... complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)(2) antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in theculture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.Vir: International immunology. - ISSN 0953-8178 (Letn. 13, št. 2, 2001, str. 203-210)Vrsta gradiva - članek, sestavni delLeto - 2001Jezik - angleškiCOBISS.SI-ID - 13022169
Avtor
Praprotnik, Sonja |
Blank, Miri |
Levy, Yair |
Sigal, Tavor |
Boffa, Marie-Claire |
Weksler, Babette |
Eldor, Amiram |
Shoenfeld, Yehuda
Teme
Purpura, thrombotic thrombocytopenic |
Immunology |
Autoantibodies |
Endothelium, vascular |
Immunology |
Plasmapheresis |
IgG |
Interleukin-6 |
Cell line |
Immunoglobulins, fab |
Von Willebrand factor |
Vascular cell adhesion molecule-1
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