Impaired alveolar macrophage function in smoke inhalation injury.
The high incidence of both bacterial pneumonia and the adult respiratory distress syndrome (ARDS) associated with smoke inhalation injury (SII) may result, at least in part, from smoke-induced injury to the alveolar macrophage (AM). Specifically, we hypothesized that AM antimicrobial function, ability to phagocytose apoptotic PMNs, and capacity to prevent apoptosis in PMNs are impaired by smoke. To test these hypotheses, AMs were harvested by bronchoalveolar lavage from sheep before and 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 their wells, whereas smoke-exposed AMs (SAMs) ingested only 60 +/- 8%. NAMs killed 80 +/- 8% of PSA ingested, whereas SAMs killed only 56 +/- 16% (P < 0.05). When sheep PMNs, allowed to undergo apoptosis, were incubated 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 markedly prevented apoptosis and augmented PMN survival relative to the unconditioned and SAM-conditioned media (P < 0.05). The poor antimicrobial function known to be characteristic of apoptotic PMNs, together with the directly impaired antimicrobial function of AMs, may contribute to the infectious complications of SII. If the PMNs recruited to the lung in SII are not properly supported by the AMs following smoke injury, large numbers may undergo apoptosis. If not properly disposed of by these SAMs, the apoptotic PMNs could eventually lyse, releasing tissue toxins, resulting in escalation of lung injury and leading to ARDS.
Herlihy
J P
JP
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston 02174.
Vermeulen
M W
MW
Joseph
P M
PM
Hales
C A
CA
D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002469:Cell Separation; D002470:Cell Survival; D017077:Culture Media, Conditioned; D016676:Macrophages, Alveolar / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010587:Phagocytosis; D012016:Reference Values; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000473:pathology / Q000503:physiopathology*
D017077:Culture Media, Conditioned