DEPLETION OF ALVEOLAR MACROPHAGES BY LIPOSOME-ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE
DEPLETION OF ALVEOLAR MACROPHAGES BY LIPOSOME-ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE
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DOI：
10.1152/jappl.1993.74.6.2812
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发表时间：
1993-06-01
影响因子：
3.3
通讯作者：
TSAN, MF
中科院分区：
文献类型：
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作者：
BERG, JT;LEE, ST;TSAN, MF
肺泡巨噬细胞（Alveolar macrophages， AM）在肺生物学中起着重要作用。在这项研究中，我们证明了气管内注入脂质体包裹的二氯甲基二膦酸盐（cl2mdp -脂质体）选择性地消耗了大鼠的AMs。注射单剂量的Cl2MDP-脂质体（80 μ mol含1.34 μ mol的Cl2MDP），而不注射含有磷酸盐缓冲盐水的脂质体，可在1天内开始并持续5天，减少bb0 - 70%的AMs。有轻微但明显的肺泡内炎症反应。Cl2MDP的注入也导致了AMs的耗竭；然而，它也引起肺泡上皮细胞的细胞质水肿。cl2mdp -脂质体对AMs的消耗可显著降低内毒素诱导的中性粒细胞（多形核淋巴细胞）募集和肿瘤坏死因子释放到肺泡间隙，提示内毒素诱导的中性粒细胞募集和肿瘤坏死因子释放依赖于AMs。该模型将为研究am的体内功能及其在各种生理和病理条件下的作用提供科学依据。
Alveolar macrophages (AM) play an important role in lung biology. In this study, we demonstrated that tracheal insufflation of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP-liposome) selectively depleted AMs in rats. Insufflation of a single dose of Cl2MDP-liposomes (80 mul containing 1.34 mumol of Cl2MDP) but not liposomes containing phosphate-buffered saline resulted in >70% depletion of AMs starting within 1 day and lasting for >5 days after insufflation. There was a slight but significant intra-alveolar inflammatory response. Insufflation of Cl2MDP also resulted in depletion of AMs; however, it caused cytoplasmic edema of alveolar epithelial cells as well. Depletion of AMs by Cl2MDP-liposomes markedly reduced the endotoxin-induced neutrophil (polymorphonuclear lymphocyte) recruitment and the release of tumor necrosis factor into the alveolar space, suggesting that endotoxin-induced neutrophil recruitment and tumor necrosis factor release were dependent on AMs. This AM-depleted animal model will be useful for studying the in vivo functions of AMs and their role in various physiological and pathological conditions.