HLA-DR - Mediated Signals for Hematopoiesis and Induction of Apoptosis Involve But Are Not Limited to a Nitric Oxide Pathway

摘要: Cross-linking of major histocompatibility complex (MHC) class II antigens by anti-HLA-DR monoclonal antibody (MoAb; H81.9; IgG2a) results in inhibition hematopoiesis canine and human models. Inhibition is associated with apoptosis a proportion marrow cells. Since murine macrophages cross-linking triggers nitric oxide (NO) production, NO thought to affect regulation hematopoiesis, we investigated whether was involved our In J774 monocytes/macrophages, MoAb H81.9 did induce NO. production blocked NG-monomethyl-L-arginine (NMMA), an inhibitor synthase (NOS), the antioxidant N-acetylcysteine (NAC). long-term cultures (LTMCs) enriched monocytes, however, no measurable increase noted after exposure. Nevertheless, NAC protected LTMCs against induced hematopoiesis. Therefore, determined effect exogenous donator, sin-1 (3-morpholinosydnonimine), on apoptosis. Sin-1 at concentrations ≥100 μg/mL inhibited apoptosis; low (1 μg/mL), stimulated generation colony-forming unit granulocyte-macrophage. Combined treatment 100 resulted profound both LTMCs, had additive At 1 counteracted The LTMC largely prevented NAC. These are consistent hypothesis that HLA-DR mediated involve oxidative stress. However, biphasic response suggests regulatory network possibly related differences sensitivity distinct subpopulations Signals addition appear be