Oosting R S, van Bree L, van Iwaarden J F, van Golde L M, Verhoef J
Department of Inhalation Toxicology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Am J Physiol. 1990 Aug;259(2 Pt 1):L87-94. doi: 10.1152/ajplung.1990.259.2.L87.
Hydrogen peroxide (H2O2) inhibited phagocytosis and superoxide anion production by rat alveolar macrophages. The inhibition was irreversible and concentration and exposure time dependent. The potential relationship between H2O2-induced biochemical perturbations and impaired alveolar macrophage phagocytic functions was investigated. Alveolar macrophage viability and Fc receptor binding capacity were not affected by H2O2. There was probably no correlation between a H2O2-induced rise in cytosolic [Ca2+] ([Ca2+]i) and the impairment of phagocytosis by alveolar macrophages, as was suggested by the following findings. First, the H2O2-induced rise in [Ca2+]i could be inhibited by chelation of extracellular Ca2+, whereas the H2O2-induced impairment of phagocytosis could not. Second, the H2O2-induced rise in [Ca2+]i was reversible, whereas the impairment of phagocytosis was not. And finally, a rise in [Ca2+]i by incubation of alveolar macrophages with the calcium ionophore A23187 did not affect phagocytosis. Various experiments suggested that ATP depletion may play an important role in the H2O2 toxicity for alveolar macrophages. Comparable concentrations of H2O2 caused an irreversible decrease both in cellular ATP and in phagocytosis and superoxide production by alveolar macrophages. In addition, time course of ATP depletion and induction of impaired alveolar macrophage function were similar. In view of the fact that the strong oxidant H2O2 may react with a large variety of biological substances, possible other toxic lesions may not be excluded as underlying mechanism for H2O2-induced inhibition of phagocytic functions of alveolar macrophages.
过氧化氢（H2O2）可抑制大鼠肺泡巨噬细胞的吞噬作用和超氧阴离子生成。这种抑制作用是不可逆的，且具有浓度和暴露时间依赖性。我们研究了H2O2诱导的生化扰动与肺泡巨噬细胞吞噬功能受损之间的潜在关系。H2O2对肺泡巨噬细胞的活力和Fc受体结合能力没有影响。如下发现提示，H2O2诱导的胞质[Ca2+]（[Ca2+]i）升高与肺泡巨噬细胞吞噬功能受损之间可能没有相关性。首先，细胞外Ca2+螯合可抑制H2O2诱导的[Ca2+]i升高，而H2O2诱导的吞噬作用受损却不受影响。其次，H2O2诱导的[Ca2+]i升高是可逆的，而吞噬作用受损则不可逆。最后，用钙离子载体A23187孵育肺泡巨噬细胞使[Ca2+]i升高并不影响吞噬作用。各种实验表明，ATP耗竭可能在H2O2对肺泡巨噬细胞的毒性作用中起重要作用。相当浓度的H2O2可导致肺泡巨噬细胞的细胞ATP、吞噬作用和超氧化物生成出现不可逆的降低。此外，ATP耗竭的时间进程与肺泡巨噬细胞功能受损的诱导过程相似。鉴于强氧化剂H2O2可能与多种生物物质发生反应，其他可能的毒性损伤作为H2O2诱导肺泡巨噬细胞吞噬功能抑制的潜在机制也不能排除。
