IMPAIRED ALVEOLAR MACROPHAGE FUNCTION IN SMOKE-INHALATION INJURY

The high incidence of both bacterial pneumonia and the adult respirato ry distress syndrome (ARDS) associated with smoke inhalation injury (S II) may result, at least in part, from smoke-induced injury to the alv eolar macrophage (AM). Specifically, we hypothesized that AM antimicro bial function, ability to phagocytose apoptotic PMNs, and capacity to prevent apoptosis in PMNs are impaired by smoke. To test these hypothe ses, AMs were harvested by bronchoalveolar ravage from sheep before an d after the animal was exposed to cotton smoke. The two populations of AMs were incubated with Pseudomonas aeruginosa (PSA) in vitro. Normal AMs (NAMs) phagocytosed a mean of 99 +/- 11% of the PSA placed in the ir wells, whereas smoke-exposed AMs (SAMs) ingested only 60 +/- 8%. NA Ms killed 80 +/- 8% of PSA ingested, whereas SAMs killed only 56 +/- 1 6% (P < 0.05). When sheep PMNs, allowed to undergo apoptosis, were inc ubated with the two AM populations, 66 +/- 3% of the NAMs and 40 +/- 6 % of the SAMs demonstrated phagocytosis of these apoptotic PMNs (P < 0 .05). Fresh sheep PMNs were incubated in unconditioned media, NAM and SAM-conditioned media, and followed over 48 hr for the development of apoptosis and maintenance of viability. The NAM-conditioned media mark edly prevented apoptosis and augmented PMN survival relative to the un conditioned and SAM-conditioned media (P < 0.05). The poor antimicrobi al function known to be characteristic of apoptotic PMNs, together wit h the directly impaired antimicrobial function of AMs, may contribute to the infectious complications of SII. If the PMNs recruited to the l ung in SII are not properly supported by the AMs following smoke injur y, large numbers may undergo apoptosis. if not properly disposed of by these SAMs, the apoptotic PMNs could eventually lyse, releasing tissu e toxins, resulting in escalation of lung injury and leading to ARDS. (C) 1995 Wiiey-Liss, Inc.