Role of nitric oxide in hematosuppression and benzene-induced toxicity

It is becoming increasingly apparent that nitric oxide plays a multifunctional role in regulating inflammatory processes in the body. Although nitric oxide and its oxidation products are cytotoxic toward certain pathogens, they can also cause tissue injury and suppress proliferation. Cytokines and growth factors released at sites of inflammation or injury stimulate both immune and nonimmume cells to produce nitric oxide. Nowhere in the body is this more detrimental than in the bone marrow, for the continuous production of hematopoietic precursors is essential for normal blood cell maturation. Our laboratories have discovered that, in response to inflammatory mediators, bone marrow cells readily produce nitric oxide. Nitric oxide production is enhanced by hematopoietic growth factors including interleukin-3, macrophage colony stimulating factor, and granulocyte-macrophage colony-stimulating factor. When bone marrow cells produce nitric oxide, hematopoiesis is impaired, an effect that is potentiated by colony-stimulating factors. Treatment of mice with benzene, which suppresses bone marrow cell development, was found to markedly enhance the ability of bone marrow cells to produce nitric oxide in response to inflammatory mediators alone and in combination with hematopoietic growth factors. Taken together, these data suggest that nitric oxide may be an important mediator of benzene-induced bone marrow suppression.