Impaired alveolar macrophage function in smoke inhalation injury

Abstract

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.

Cotton Smoke Inhalation Primes Alveolar Macrophages for Tumor Necrosis Factor-α Production and Suppresses Macrophage Antimicrobial Activities

“…Smoke-exposed m demonstrated an ∼70% reduction in phagocytosis of opsonized S. aureus and an ∼20% decrease in adherence to solid substratum (albeit a nonphysiological surface, plastic). Similar effects have been observed for alveolar m of other species after inhalation of different types of smoke [2,16,18]. Further, we found comparable effects on rabbit alveolar m within 70 min of exposure to cotton smoke [6].…”

Apoptotic Neutrophils Undergoing Secondary Necrosis Induce Human Lung Epithelial Cell Detachment

“…This important observation implies that the balance between neutrophil apoptosis and their phagocytic clearance can be disturbed. Indeed, this possibility is supported by two further ex vivo studies that specifically verified the functional impairment of alveolar macrophages, both in clearing apoptotic neutrophils in children suffering from recurrent respiratory tract infections, and in an animal model of experimental smoke inhalation injury [26,43].…”

“…In patients with cystic fibrosis, Pseudomonas aeruginosa products have been reported to inhibit macrophage phagocytosis [36,37]. Moreover, the ability of alveolar macrophages to phagocytose apoptotic neutrophils was found to be significantly impaired in smoke inhalation injury, a condition associated with a high incidence of both bacterial pneumonia and adult respiratory distress syndrome (ARDS) [26], and in children suffering recurrent respiratory tract infections [43]. Other investigations have suggested that macrophages which had previously ingested apoptotic cells subsequently have impaired ingestion capacity [18].…”

Lung involvement in accident victims: report of three cases

“…The risk for pneumonia is increased due to impaired function of alveolar macrophages, polymorphonuclear leukocytes, and mucociliary clearance mechanisms. 11,12 Chest radiography is typically obtained in the initial evaluation of the injured patient but has low sensitivity for inhalation injury. Most patients with inhalation injury have a normal chest radiograph at presentation and presence of pulmonary opacities on initial chest films has been implicated as a marker of severe injury and a poor prognosis.…”