期刊
AIDS
卷 20, 期 13, 页码 1713-1720出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.aids.0000242817.88086.8c
关键词
HIV-1; megakaryocytopoiesis; antiretroviral therapy; hematopoietic stem cells; cell culture
Objective: To address the mechanisms of the thrombocytopoietic dysfunction that may follow HIV infection and to compare peripheral blood and bone marrow as sources of CD34 progenitor cells in HIV-infected patients. Methods: The study used CD34 progenitor cells from 20 previously untreated HIV-infected individuals, 20 HIV-infected individuals treated with antiretroviral therapy and a control group of 20 HIV-uninfected healthy individuals to examine in-vitro mega-karyocytopoiesis. There were no hematological abnormalities at baseline in the study groups. CD34 progenitor cells derived from peripheral blood and bone marrow were purified and cultured in medium containing thrombopoietin, interleukin-3, and interleukin-6. HIV-1 plasma viral load was determined by b-DNA technique. Expression of receptors for thrombopoietin, interleukin-3, and interleukin-6 was assessed on CD34 cells by flow cytometry, and numbers of receptors per single cell were calculated by Quanticalc software. Results: Growth of megakaryocytopoietic colony-forming units (CFU-MK) were impaired in untreated HIV-infected individuals despite normal platelet counts. Viral load levels inversely correlate with CFU-MK growth and platelet counts. Antiretroviral drug-treated individuals showed normal megakaryocyte development. Similar results were obtained whether the CD34 progenitor cells derived from peripheral blood or bone marrow. Conclusions: These findings suggest that megakaryocyte differentiation is impaired before the onset of overt thrombocytopenia in HIV-infected patients and provide evidence for a direct link between viral replication and perturbed megakaryocytopoiesis, which appears to be prevented and/or restored by antiretroviral therapy. The results indicate that peripheral blood represents a suitable source of CD34 hematopoietic progenitors for studies of mega karyocytopoiesis in HIV disease. (c) 2006 Lippincott Williams & Wilkins.
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