Herlihy J P, Vermeulen M W, Joseph P M, Hales C A
Pulmonary and Critical Care Unit, Massachusetts General Hospital, Boston 02174.
J Cell Physiol. 1995 Apr;163(1):1-8. doi: 10.1002/jcp.1041630102.
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.
与烟雾吸入性损伤（SII）相关的细菌性肺炎和成人呼吸窘迫综合征（ARDS）的高发病率，至少部分可能是由于烟雾对肺泡巨噬细胞（AM）造成的损伤所致。具体而言，我们推测烟雾会损害AM的抗菌功能、吞噬凋亡中性粒细胞的能力以及防止中性粒细胞凋亡的能力。为了验证这些假设，在绵羊暴露于棉花烟雾之前和之后，通过支气管肺泡灌洗收集AM。将这两组AM在体外与铜绿假单胞菌（PSA）一起孵育。正常AM（NAM）吞噬了平均99±11%置于其孔中的PSA，而暴露于烟雾的AM（SAM）仅摄取了60±8%。NAM杀死了80±8%摄取的PSA，而SAM仅杀死了56±16%（P<0.05）。当使绵羊中性粒细胞发生凋亡并与这两组AM一起孵育时，66±3%的NAM和40±6%的SAM表现出对这些凋亡中性粒细胞的吞噬作用（P<0.05）。将新鲜的绵羊中性粒细胞在未处理的培养基、NAM和SAM处理的培养基中孵育，并在48小时内监测凋亡的发生和活力的维持。与未处理的和SAM处理的培养基相比，NAM处理的培养基显著预防了凋亡并增强了中性粒细胞的存活（P<0.05）。已知凋亡中性粒细胞具有较差的抗菌功能，再加上AM直接受损的抗菌功能，可能会导致SII的感染性并发症。如果在烟雾损伤后，SII中募集到肺内的中性粒细胞没有得到AM的适当支持，大量中性粒细胞可能会发生凋亡。如果这些SAM不能妥善处理凋亡的中性粒细胞，凋亡的中性粒细胞最终可能会裂解，释放组织毒素，导致肺损伤加剧并引发ARDS。
