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

Shengjun Wang, R. Clark Lantz, Mary W. Vermeulen, Guan Jie Chen, Veronica Breceda, Raymond F. Robledo, Allison M. Hays, Scott Young, Mark L. Witten

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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-α (TNF-α), 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-α 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-α 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-α release, in addition to its primary antioxidative mechanism.

Original languageEnglish (US)
Pages (from-to)464-469
Number of pages6
JournalToxicology and Industrial Health
Issue number5
StatePublished - Jun 1999


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

ASJC Scopus subject areas

  • Toxicology
  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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