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Failure to establish long‐term marrow cultures from immunodeficient mice (MAIDS): effect of zidovudine in vitro
Author(s) -
Tse KamFai,
Hughes Nedda K.,
Gallicchio Vincent S.
Publication year - 1993
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.53.6.658
Subject(s) - zidovudine , biology , bone marrow , haematopoiesis , indinavir , cfu gm , virus , virology , megakaryocyte , in vitro , immunology , myeloid , stromal cell , progenitor cell , peripheral blood mononuclear cell , murine leukemia virus , stem cell , cancer research , viral disease , sida , microbiology and biotechnology , biochemistry
We report here the results of studies examining the ability of zidovudine (AZT) to influence the establishment and maintenance of long‐term marrow cultures (LTMG) using marrow from murine immunodeficient mice (MAIDS). Normal C57BL6 mice were infected with LP‐BM5 (MuLV) immunodeficiency virus (10μg total protein) intraperitoneally. Five weeks after viral infection, mice were sacrificed and marrow was harvested from normal non‐virus‐infected and virus‐infected animals. LTMC were established in the presence or absence of dose escalation of AZT, that is, 10 −6 , 5 × 10 −7 , and 10 −7 M in vitro. Compared with controls prepared from normal bone marrow, LTMC using MAIDS‐infected marrow failed to establish and subsequently release supernatant‐derived mononuclear cells. The addition of AZT was ineffective in either establishing LTMC or consistently producing mononuclear cells. Measurements of erythroid (BFU‐E), myeloid (CFU‐GM), and megakaryocyte (CFU‐Meg) precursors were all depressed and none were observed after 5 weeks of culture. Treatment with AZT failed to reverse this depression of stem cell progenitors. Microscopic examination of cultures at 10 weeks demonstrated a failure of MAIDS‐LTMC to establish an adequate stromal layer compared to LTMC prepared form non‐virus‐infected controls. This data indicate that LP‐BM5 MuLV infection alters the establishment of a normal functioning hematopoietic microenvironment or stroma. Acknowledging that important differences between MAIDS and human AIDS exist, the implications of these findings concerning the establishment of the immunodeficiency disease state in human immunodeficiency virus infection is discussed.