Cotton smoke inhalation primes alveolar macrophages for tumor necrosis factor-alpha production and suppresses macrophage antimicrobial activities.
The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mphi). Smoke inhalation led to dose-dependent impairment of respiratory gas exchange by 48 h postexposure and pulmonary edema by 96 h. Maximal effects were observed in animals ventilated with 54 breaths of cotton smoke (3-min exposure, 18 breaths/min). Macrophages were obtained at 48 h postexposure by bronchoalveolar lavage of rabbits subjected to 54 breaths of smoke or room air (control). Phagocytosis of opsonized bacteria and adherence to solid substratum were reduced in smoke-exposed mphi. Smoke inhalation primed mphi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed mphi were also primed for TNF-alpha release induced by phorbol myristate acetate, which suggests that the priming event occurred downstream of protein kinase C activation in the signal transduction pathway. Further, smoke exposure attenuated the inhibitory effects of phosphodiesterase inhibitors on LPS-induced TNF-alpha release. Thus, the priming event may be mediated through cAMP and/or protein kinase A. The data indicate that cotton smoke inhalation suppresses the antimicrobial activities of alveolar mphi and can lead to excessive mphi production of TNF-alpha. These mphi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0876, USA.
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Bidani
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CZ
Wang
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Heming
D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D001826:Body Fluids / Q000378:metabolism; D015169:Colony Count, Microbial; D003368:Gossypium; D006863:Hydrogen-Ion Concentration; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010587:Phagocytosis / Q000502:physiology*; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D011817:Rabbits; D012906:Smoke / Q000009:adverse effects*; D015208:Smoke Inhalation Injury / Q000209:etiology / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D012906:Smoke; D014409:Tumor Necrosis Factor-alpha