STIMULATION OF NITRIC-OXIDE PRODUCTION IN RAT LUNG LAVAGE CELLS BY ANTI-MAC-1-BETA ANTIBODY - EFFECTS OF OZONE INHALATION

Acute inhalation of the pulmonary irritant ozone is associated with an inflammatory response characterized by increased numbers of macrophag es in the lung that release elevated quantities of nitric oxide. The a ccumulation of phagocytes in the lung is dependent on expression of le ukocyte adhesion molecules including Mac-1. In the present studies, we determined whether activation of the Mac-1 receptor is involved in re gulating nitric oxide production by lung phagocytes, and whether this response is modified following acute ozone inhalation. Cells were isol ated from the lung by bronchoalveolar lavage 48 h after exposure of fe male Sprague-Dawley rats to air or ozone (2 parts per million, for 3 h ). Anti-Mac-1 beta antibody, but not anti-Mac-1 alpha antibody, stimul ated nitric oxide production by cells from both air- and ozone-exposed animals. Cells from ozone-exposed rats produced more nitric oxide and expressed greater quantities of inducible nitric oxide synthase mRNA than did cells from air-exposed animals. Production of nitric oxide in response to anti-Mac-1 beta was also found to be augmented by cross-l inking of the Mac-1 beta receptor. Pretreatment of lavage cells with g ranulocyte/macrophage colony-stimulating factor (GM-CSF), which activa tes phagocytes, enhanced the expression of Mac-1 beta and increased an ti-Mac-1 beta-induced nitric oxide production by the cells. Lavage cel ls from ozone-exposed animals were more responsive to GM-CSF than were cells from control animals. Taken together, these data suggest that t he Mac-1 beta adhesion molecule may contribute to phagocyte activation and mediator release during ozone-induced inflammatory reactions in t he lung.