Functional alterations of alveolar macrophages subjected to smoke exposure and antioxidant lazaroids.
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-alpha (TNF-alpha), 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-alpha 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-alpha 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-alpha release, in addition to its primary antioxidative mechanism.
Wang
S
S
The Joan B. and Donald R. Diamond Lung Injury Laboratory, Department of Pediatrics, University of Arizona Health Sciences Center, Tucson 85724-5073, USA.
Lantz
R C
RC
Vermeulen
M W
MW
Chen
G J
GJ
Breceda
V
V
Robledo
R F
RF
Hays
A M
AM
Young
S
S
Witten
M L
ML
D000336:Aerosols / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D005742:Gasoline / Q000633:toxicity; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D011076:Polycarboxylate Cement / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D016897:Respiratory Burst / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D015208:Smoke Inhalation Injury / Q000378:metabolism / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms; D013256:Steroids / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000336:Aerosols; D000975:Antioxidants; D017077:Culture Media, Conditioned; D005742:Gasoline; D011076:Polycarboxylate Cement; D012333:RNA, Messenger; D012906:Smoke; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C069980:U 75412E; C005506:polycarbonate