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Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona

R. Clark Lantz

Departments of Cell Biology and Anatomy, Center for Toxicology, Tucson, Arizona

Mary W. Vermeulen

Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston, Massachusetts, Harvard Medical School, Boston, Massachusetts

Guan Jie Chen

Departments of Cell Biology and Anatomy, Center for Toxicology, Tucson, Arizona

Veronica Breceda

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona

Raymond F. Robledo

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona

Allison M. Hays

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona

Scott Young

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona

Mark L. Witten

The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson, Arizona, mwitten{at}peds.arizona.edu

Acute inhalation of diesel fuel-polycarbonate plastic (DFPP) smoke causes severe lung injury, leading to acute respiratory distress syndrome (ARDS) and death. It has been reported that the initiation of acute lung injury is associated with the activation of pulmonary alveolar macrophages (PAM). To further explore the pathogenesis, alveolar macrophages (AM) of New Zealand rabbits ventilated and exposed to a 60 tidal volume of DFPP smoke in vivo were recovered at 1 h post-smoke. Smoke exposure induced significant increases in both mRNA and protein levels for PAM tumor necrosis factor- (TNF-), when compared to smoke control. Smoke also induced a biphasic response (inhibited at 2 h, enhanced at 24 h after cell isolation) in the production of superoxide (O₂^–) by PAM. However, aerosolized lazaroid, U75412E (1.6 mg/kg body weight), significantly attenuated smoke-induced expression in AM TNF- at the protein level but not at the mRNA level, and smoke-induced changes in AM production of O₂^–. This study suggests that highly expressing AM TNF- following smoke may be a key contributor to the cascade that establishes an acute injury process and exacerbates oxidant-derived cell injury. Whereas, the lazaroid may ameliorate smoke-induced lung injury by attenuating AM TNF- release, in addition to its primary antioxidative mechanism.

Key Words: alveolar macrophages • lazaroids • lung injury • smoke inhalation • superoxide • tumor necrosis factor

Toxicology and Industrial Health, Vol. 15, No. 5, 464-469 (1999)
DOI: 10.1177/074823379901500501


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