Crowell R E, Hallin G, Heaphy E, Mold C
Department of Medicine, University of New Mexico School of Medicine, albuquerque 87131.
Am J Respir Cell Mol Biol. 1995 Feb;12(2):190-5. doi: 10.1165/ajrcmb.12.2.7865216.
Lower respiratory tract exposure to high oxygen (O2) concentrations is known to induce changes in pulmonary function through effects on several cell types located within the lung parenchyma, including pulmonary macrophages (PM). We studied the effects of hyperoxic exposure on phagocytosis via Fc-gamma receptors (FcR) on isolated murine PM. PM cultured in hyperoxic conditions exhibited little change in ingestion via FcR for up to 96 h, compared with significant increases in ingestion by PM cultured in 21% O2 over the same time period. This suppression was reversible and occurred whether 50 or 100% O2 concentrations were used for hyperoxic exposure. Addition of the potent macrophage-activating agent interferon-gamma (IFN-gamma) to cultured PM further increased FcR-mediated phagocytosis in normoxic PM but had no effect on PM cultured in 100% O2. Analysis of FcR expression by flow cytometry using monoclonal antibodies specific for two different FcR classes revealed that culture in normoxic conditions increased surface expression of both FcR classes. Hyperoxic culture inhibited up-regulation of the high-affinity FcR but did not affect low-affinity FcR up-regulation, suggesting that hyperoxic effects were not due solely to effects on regulation of FcR expression. However, hyperoxic exposure completely suppressed FcR-mediated actin polymerization. These findings suggest that hyperoxic exposure impairs PM ability to increase FcR-mediated phagocytic activity after appropriate stimulation, which could impair the lung's defenses against infection.
已知下呼吸道暴露于高氧（O₂）浓度会通过影响肺实质内的几种细胞类型，包括肺巨噬细胞（PM），从而诱导肺功能发生变化。我们研究了高氧暴露对分离的小鼠PM通过Fc-γ受体（FcR）进行吞噬作用的影响。与在21% O₂中培养的PM在同一时间段内摄取量显著增加相比，在高氧条件下培养的PM通过FcR的摄取在长达96小时内几乎没有变化。这种抑制是可逆的，无论高氧暴露使用50%还是100%的O₂浓度都会发生。向培养的PM中添加强效巨噬细胞激活剂干扰素-γ（IFN-γ）可进一步增加常氧PM中FcR介导的吞噬作用，但对在100% O₂中培养的PM没有影响。使用针对两种不同FcR类别的单克隆抗体通过流式细胞术分析FcR表达，结果显示在常氧条件下培养会增加两种FcR类别的表面表达。高氧培养抑制了高亲和力FcR的上调，但不影响低亲和力FcR的上调，这表明高氧效应并非仅归因于对FcR表达调节的影响。然而，高氧暴露完全抑制了FcR介导的肌动蛋白聚合。这些发现表明，高氧暴露会损害PM在适当刺激后增加FcR介导的吞噬活性的能力，这可能会损害肺部对感染的防御能力。
