Early effects of smoke inhalation on alveolar macrophage functions

Alveolar macrophage (AM) dysfunctions have been implicated in the pathogenesis of smoke inhalation lung injury. We investigated the early (within 70 min) effects of smoke inhalation on AM. The cells were recovered by bronchoalveolar lavage from rabbits ventilated with cotton smoke for 5 min followed by O-2/room air for 60 min (smoke-exposed) or with room air in place of smoke (control). Smoke injury caused arterial blood carboxyhaemoglobin levels to increase Ii-fold and reduced arterial blood PO2 (measured similar to I h postinjury) by 25 per cent. Scanning electron micrographs revealed denudation of plasmalemmal pseudopods in smoke-exposed AM. Smoke exposure suppressed both AM adherence to plastic and phagocytosis of opsonized bacteria. Basal superoxide (O-2(-)) production was elevated in smoke-exposed AM, compared with controls whereas PMA-stimulated O-2(-) production was unaffected. Smoke-exposed AM had reduced basal secretion of tumour necrosis factor-alpha (TNF-alpha) but displayed a greater TNF response to stimulation with LPS than did control cells. LPS-stimulated TNF-alpha releases from control and smoke-exposed AM were suppressed by phosphodiesterase inhibitors pentoxifylline and theophylline, and were enhanced by the lipoxygenase inhibitor, MK886. The early responses of AM to smoke inhalation lung injury are consistent with activation of O-2(-) production and priming of TNF-alpha release, concurrent with a functional down regulation of phagocytosis.