Bidani A, Wang C Z, Heming T A
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0876, USA.
Lung. 1998;176(5):325-36. doi: 10.1007/pl00007614.
The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mphi). Smoke inhalation led to dose-dependent impairment of respiratory gas exchange by 48 h postexposure and pulmonary edema by 96 h. Maximal effects were observed in animals ventilated with 54 breaths of cotton smoke (3-min exposure, 18 breaths/min). Macrophages were obtained at 48 h postexposure by bronchoalveolar lavage of rabbits subjected to 54 breaths of smoke or room air (control). Phagocytosis of opsonized bacteria and adherence to solid substratum were reduced in smoke-exposed mphi. Smoke inhalation primed mphi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed mphi were also primed for TNF-alpha release induced by phorbol myristate acetate, which suggests that the priming event occurred downstream of protein kinase C activation in the signal transduction pathway. Further, smoke exposure attenuated the inhibitory effects of phosphodiesterase inhibitors on LPS-induced TNF-alpha release. Thus, the priming event may be mediated through cAMP and/or protein kinase A. The data indicate that cotton smoke inhalation suppresses the antimicrobial activities of alveolar mphi and can lead to excessive mphi production of TNF-alpha. These mphi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.
本研究确定了吸入棉花烟雾对肺泡巨噬细胞（Mφ）功能的影响。吸入烟雾在暴露后48小时导致呼吸气体交换出现剂量依赖性损伤，在96小时导致肺水肿。在用54次棉花烟雾呼吸（3分钟暴露，18次呼吸/分钟）通气的动物中观察到最大效应。在暴露后48小时，通过对接受54次烟雾呼吸或室内空气（对照）的兔子进行支气管肺泡灌洗来获取巨噬细胞。暴露于烟雾的Mφ对调理素化细菌的吞噬作用和对固体基质的黏附作用降低。吸入烟雾使Mφ对脂多糖（LPS）诱导的肿瘤坏死因子-α（TNF-α）释放产生预激作用。暴露于烟雾的Mφ对佛波酯肉豆蔻酸酯诱导的TNF-α释放也产生预激作用，这表明预激事件发生在信号转导途径中蛋白激酶C激活的下游。此外，烟雾暴露减弱了磷酸二酯酶抑制剂对LPS诱导的TNF-α释放的抑制作用。因此，预激事件可能通过环磷酸腺苷（cAMP）和/或蛋白激酶A介导。数据表明，吸入棉花烟雾会抑制肺泡Mφ的抗菌活性，并可导致Mφ过度产生TNF-α。预计这些Mφ效应会导致与吸入烟雾损伤相关的病理生理异常。
