Am. J. Respir. Cell Mol. Biol., Vol 14, No. 4, Apr 1996, 327-333.
Stimulation of nitric oxide production in rat lung lavage cells by anti- Mac-1beta antibody: effects of ozone inhalation
KJ Pendino, CR Gardner, S Quinones and DL Laskin
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855-0789, USA.
Acute inhalation of the pulmonary irritant ozone is associated with an
inflammatory response characterized by increased numbers of macrophages in
the lung that release elevated quantities of nitric oxide. The accumulation
of phagocytes in the lung is dependent on expression of leukocyte adhesion
molecules including Mac-1. In the present studies, we determined whether
activation of the Mac-1 receptor is involved in regulating nitric oxide
production by lung phagocytes, and whether this response is modified
following acute ozone inhalation. Cells were isolated from the lung by
bronchoalveolar lavage 48 h after exposure of female Sprague-Dawley rats to
air or ozone (2 parts per million, for 3 h). Anti-Mac-1beta antibody, but
not anti-Mac-1alpha antibody, stimulated 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-1beta was also found to
be augmented by cross-linking of the Mac-1beta receptor. Pretreatment of
lavage cells with granulocyte/macrophage colony-stimulating factor (GM-
CSF), which activates phagocytes, enhanced the expression of Mac-1beta and
increased anti-Mac-1beta-induced nitric oxide production by the cells.
Lavage cells from ozone-exposed animals were more responsive to GM-CSF than
were cells from control animals. Taken together, these data suggest that
the Mac-1beta adhesion molecule may contribute to phagocyte activation and
mediator release during ozone-induced inflammatory reactions in the lung.
