Cytomegalovirus inhibits the engraftment of donor bone marrow cells by downregulation of hemopoietin gene expression in recipient stroma
Journal of virology. Bd. 72. H. 6. Washington: American Society for Microbiology 1998 S. 5006 - 5015
Erscheinungsjahr: 1998
ISBN/ISSN: 0022-538X
Publikationstyp: Zeitschriftenaufsatz
Sprache: Englisch
Doi/URN: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC110063/pdf/jv005006.pdf
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Inhaltszusammenfassung
Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often associated with BM graft failure. There are two possible reasons for such a correlation. First, a poor hematopoietic reconstitution of unrelated etiology could promote the progression of CMV infection by the lack of immune control, Alternatively, CMV infection could interfere with the engraftment of donor BR I cells in recipient BM stroma. Evidence for a causative role of CMV in BR I aplasia came from studies in lon...Cytomegalovirus (CMV) disease after bone marrow (BM) transplantation is often associated with BM graft failure. There are two possible reasons for such a correlation. First, a poor hematopoietic reconstitution of unrelated etiology could promote the progression of CMV infection by the lack of immune control, Alternatively, CMV infection could interfere with the engraftment of donor BR I cells in recipient BM stroma. Evidence for a causative role of CMV in BR I aplasia came from studies in long-term BM cultures and from the murine in vivo model of CMV-induced aplastic anemia. A deficiency in the expression of essential stromal hemopoietins, such as stem cell factor (SCF), has indicated a functional insufficiency of the stromal microenvironment, It remained open to question whether CMV mediates a negative regulation of hemopoietin gene expression (the downregulation model) or whether it causes the default of a positive regulator (the lack-of-induction model). Further, even though implicitly assumed, it has never been formally documented that CMV directly interferes with the engraftment of a BM cell transplant. We addressed these problems in a murine model of CMV infection after experimental male-into-female BM transplantation. The data indicate that the downregulation model applies. Quantitation of the male-sex-determining gene tdy demonstrated an impaired engraftment of donor BM cells in the BM stroma of the female recipients. This graft failure was reflected by a diminished population of SCF-receptor-expressing hematopoietic progenitor cells and correlated with a reduced level of stromal SCF gene expression. Interestingly, high doses of BM cells protected against stromal insufficiency by a mechanism unrelated to control of infection.» weiterlesen» einklappen
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Medizin