Stimulation of nitric oxide production in rat lung lavage cells by anti-Mac-1beta antibody: effects of ozone inhalation.
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.
Pendino
K J
KJ
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855-0789, USA.
Gardner
C R
CR
Quinones
S
S
Laskin
D L
DL
D000280:Administration, Inhalation; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D010126:Ozone / Q000008:administration & dosage / Q000494:pharmacology*; D010586:Phagocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D009569:Nitric Oxide; D010126:Ozone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor