Cotton smoke inhalation primes alveolar macrophages for tumor necrosis factor-α production and suppresses macrophage antimicrobial activities

The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (m phi). 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 m phi. Smoke inhalation primed m phi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed m phi 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 m phi and can lead to excessive m phi production of TNF-alpha. These m phi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.