Acrolein-induced cell death in human alveolar macrophages.
Acrolein is an environmental air pollutant that is known to suppress respiratory host defense against infections. The mechanism of the decrease in host defense is not yet clear. In this study, the effects of acrolein on human alveolar macrophages and their function were examined. Acrolein caused dose-dependent cytotoxicity to alveolar macrophages as demonstrated by the induction of apoptosis and necrosis. In addition, at lower doses, acrolein caused induction of heme oxygenase 1 protein; however, stress protein 72 (SP72) was not induced. These findings demonstrated that acrolein caused a dose-dependent selective induction of a stress response, apoptosis, and necrosis in human alveolar macrophages. Macrophage function was assessed by release of cytokines in response to endotoxin stimulation. Acrolein caused a dose-dependent inhibition of release of IL-1beta, TNF-alpha, and IL-12. The inhibition of cytokine release and cytotoxicity to alveolar macrophages may in part be responsible for acrolein-induced immunosuppression of the lung.
Li
L
L
Department of Internal Medicine, Toxicology Program, University of Texas Houston Health Science 77030, USA. lili@heart.med.uth.tmc.edu
Hamilton
R F
RF
Taylor
D E
DE
Holian
A
A
D000171:Acrolein / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000187:drug effects; D051547:Heme Oxygenase-1; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology*; D008565:Membrane Proteins; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D000171:Acrolein; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1