Cotton Smoke Inhalation Primes Alveolar Macrophages for Tumor Necrosis Factor-α Production and Suppresses Macrophage Antimicrobial Activities
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The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mφ). 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 mφ. Smoke inhalation primed mφ for release of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS). Smoke-exposed mφ were also primed for TNF-α 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-α 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 mφ and can lead to excessive mφ production of TNF-α. These mφ effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.
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