Evaluation of murine leukemia virus infection as a model for thrombocytopenia of HIV/AIDS: mechanism of thrombocytopenia and modulation of thrombocytopenia by thrombopoietin.
Infection of mice with the murine leukemia virus (LP-BM5) was evaluated as a model for the thrombocytopenia of HIV/AIDS. Percent 35S incorporation into platelets, platelet size, platelet count, platelet-associated immunoglobulins (PAIgG), and megakaryocyte size and number were evaluated over a period of 3-9 weeks postinfection (PI). Thrombopoietin from human embryonic kidney cells was administered to mice 9 weeks PI, and similar indices of platelet production were measured 2, 3, and 4 days after treatment with a biological preparation of thrombopoietin (thrombocytopoiesis-stimulating factor, or TSF). Platelet counts decreased in a time-dependent fashion (p = 0.0006) following infection, reaching a nadir at 8 weeks PI (82% of control values). Percent 35S incorporation into platelets also decreased over the 9-week period (p = 0.0001), falling to 63% of control values by week 9. Additionally, platelet volume increased in a linear fashion (p = 0.01), rising to 105% of control values by week 9. No changes in PAIgG were noted over the 9-week period. Megakaryocyte numbers in the femoral marrow were decreased at 8 weeks PI (p = 0.02, 78% of control values), while increased mean megakaryocyte size (p = 0.007, 116% of controls) was noted in the same animals. Increased numbers of naked megakaryocyte nuclei were observed at 3 weeks PI (p < 0.05, 208% of control values). Administration of 2 U/mouse of a highly purified preparation of TSF to virus-infected, thrombocytopenic mice resulted in increased thrombocytopoiesis, as compared to human serum albumin-treated, virus-infected controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Sullivan
P S
PS
Department of Animal Science, College of Veterinary Medicine, University of Tennessee, Knoxville 37901, USA.
McDonald
T P
TP
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002460:Cell Line; D004195:Disease Models, Animal; D006678:HIV; D015658:HIV Infections / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000473:pathology; D006801:Humans; D007668:Kidney; D009052:Leukemia Virus, Murine; D008297:Male; D008533:Megakaryocytes / Q000166:cytology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D012044:Regression Analysis; D012192:Retroviridae Infections / Q000097:blood*; D013921:Thrombocytopenia / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D013926:Thrombopoietin / Q000627:therapeutic use*; D013997:Time Factors; D014412:Tumor Virus Infections / Q000097:blood*
D013926:Thrombopoietin