Evidence that platelet-derived microvesicles may transfer platelet-specific immunoreactive antigens to the surface of endothelial cells and CD34+ hematopoietic stem/ progenitor cells--implication for the pathogenesis of immune thrombocytopenias.
The pathogenesis and tissue damage that accompanies destruction of platelets in immune thrombocytopenias (IT) is still not understood very well and in addition to platelets, other cells (e.g. endothelial cells, CD34+ hematopoietic stem/progenitors) may also become affected. Based on our previous work that platelet antigens (e.g., CD41) may be transferred by platelet-derived microvesicles (PMV) to the surface of other cells, we asked if platelet derived-antigens, especially those that are involved in the formation of anti-platelet antibodies in IT (e.g., against antigen HPA 1 a) could be also transferred by similar mechanism. To address this issue normal human CD34+ cells, human umbilical vein-endothelial cells (HUVEC) and monocytic cell line THP-1 were incubated with PMV derived from HPA1a+ donors. We noticed that the HPA1a antigen is highly expressed on PMV-derived from the HPAla positive platelets and is transferred in PMV-dependent manner to the surface of CD34+ cells, HUVEC and monocytic THP-1 cells. These cells covered with HPA1a positive PMV but not by PMV derived from HPAla negative platelets reacted with anti-HPA1a antibodies derived from the alloimmunized pregnant women. More importantly, human hematopoietic cells that were preincubated with HPA1a+ PMV and subsequently exposed to anti-HPA 1 a serum and human NK cells, become subject to elimination by antibody dependent cell cytotoxicity ADCC. Thus, we postulate that PMV-dependent transfer of antigens may playing an important role in "expanding" the population of target cells that may be affected by anti-platelet antibodies and explain several pathologies that accompany IT (e.g. damage of endothelium, cytopenias).
Majka
Marcin
M
Dept. of Transplantation, Polish-American Institute of Pediatrics, Wielicka 265, 30-663 Krak6w, Poland. mmajka@cm-uj.krakow.pl
Kijowski
Jacek
J
Lesko
Ewa
E
Goźdizk
Jolanta
J
Zupanska
Barbara
B
Ratajczak
Mariusz Z
MZ
D018952:Antigens, CD34 / Q000032:analysis; D016824:Antigens, Human Platelet / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D039661:Integrin beta3; D015539:Platelet Activation; D011247:Pregnancy; D013234:Stem Cells / Q000276:immunology*; D013921:Thrombocytopenia / Q000276:immunology*
D018952:Antigens, CD34; D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3