急性肺损伤小鼠肺泡巨噬细胞吞噬功能降低

目的 探讨急性肺损伤（ALI）小鼠肺泡巨噬细胞吞噬功能的变化及其影响因素。方法 昆明种小鼠随机分为正常对照组、ALI模型组，脂多糖经气道滴入激发构建ALI模型小鼠；通过支气管肺泡灌洗获取肺泡巨噬细胞（AM），流式细胞术及荧光显微镜观察ALI小鼠AM吞噬功能的变化；免疫印迹与ELISA检测ALI小鼠肺组织白介素-33（IL-33）的表达和分泌情况；ELISA检测不同浓度脂多糖刺激肺泡上皮细胞株MLE-12细胞IL-33分泌的情况；采用不同浓度的脂多糖和IL-33作用正常组AM，观察这些刺激因素对AM吞噬荧光微球的影响。结果 与正常小鼠AM（75.1%±3.0）%相比，ALI小鼠AM吞噬荧光微球百分率（57.0±4.3）%明显降低，但ALI小鼠肺组织IL-33的表达和支气管肺泡灌洗液中IL-33的分泌均明显升高（P<0.05）；脂多糖（100~1000 ng/mL）促进肺泡上皮细胞IL-33分泌增加（P<0.01）；脂多糖（10~500 ng/mL）和IL-33（100 ng/mL）均明显抑制了AM的吞噬功能（P<0.05）。结论 ALI小鼠AM吞噬功能降低，这可能是由于脂多糖直接刺激AM引起，或者脂多糖激发肺泡上皮细胞产生的预警素IL-33也可抑制AM吞噬功能。

Phagocytosis of alveolar macrophages is suppressed in a mouse model oflipopolysaccharide-induced acute lung injury

Objective To investigate the changes in phagocytic function of alveolar macrophages (AMs) in mice withlipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the possible mechanism. Methods Kunming mice wererandomly divided into normal control group and ALI (induced by LPS instillation in the airway) model group. AMs wereobtained from bronchoalveolar lavage fluid in both groups, and phagocytosis of the AMs was observed using flow cytometryand fluorescence microscopy. Western blotting and ELISA were used to detect the expression and secretion of IL-33 in the lungtissue of the mice. We also detected the secretion of IL-33 by an alveolar epithelial cell line MLE-12 in response to stimulationwith different concentrations of LPS. The AMs from the normal control mice were treated with different concentrations of LPSand IL-33, and the changes in the phagocytic activity of the cells were observed. Results Compared with those in normalcontrol group, the percentage of AMs phagocytosing fluorescent microspheres was significantly decreased, and the expressionof IL-33 in lung tissue and IL-33 level in the bronchoalveolar lavage fluid were significantly increased in ALI mice (P<0.05). LPS(100-1000 ng/mL) obviously promoted the secretion of IL-33 in cultured MLE-12 cells (P<0.01). Both LPS (10-500 ng/mL) andIL-33 (100 ng/mL) significantly inhibited the phagocytic activity of the AMs from normal control mice (P<0.05). ConclusionThe phagocytic activity of AMs is weakened in ALI mice possibly due to direct LPS stimulation and the inhibitory effect of thealarmin IL-33 produced by LPS-stimulated alveolar epithelial cells.