HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF BONE-MARROW ENDOTHELIUM REDUCES INDUCTION OF STROMAL HEMATOPOIETIC GROWTH-FACTORS

The majority of human immunodeficiency virus (HIV)-seropositive patien ts develop bone marrow abnormalities associated with hematopoietic mal function during the progression of disease. One important manifestatio n of HIV-associated hematopoietic dysfunction is that after myelosuppr ession, bone marrow recovery, a process known to be mediated in part b y the production of stromal cell-derived hematopoietic growth factors, is impaired. We sought to test the hypothesis that bone marrow stroma l cells are infected by HIV-1 in vivo and that production of certain s tromal cell-derived hematopoietic growth factors is deficient as a con sequence. In this report, we demonstrate that bone marrow microvascula r endothelial cells (MVEC), a key element of the stroma, are the predo minant cells infected by HIV (5% to 20%) in bone marrow stromal cultur es obtained from 11 consecutive HIV-seropositive patients, Although HI V-infected stromal cultures enriched for MVEC constitutively express n ormal levels of interleukin (IL)-4, IL-6, granulocyte (G)-colony-stimu lating factor (CSF), granulocyte-macrophage (GM)-CSF, tumor necrosis f actor (TNF)-alpha, transforming growth factor (TGF)-beta, and Steel fa ctor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly re duced in these cultures. These observations suggest that HIV infection of bone marrow MVEC reduces the capacity of hematopoietic stroma to r espond to regulatory signals that normally augment blood cell producti on during periods of increased demand. (C) 1996 by The American Societ y of Hematology.