Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly
Monocytes recruited to the lungs of mice during immune inflammation ingest apoptotic cells poorly
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DOI：
10.1165/rcmb.2004-0108oc
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发表时间：
2005-02-01
影响因子：
6.4
通讯作者：
Curtis, JL
中科院分区：
文献类型：
--
作者：
Jennings, JH;Linderman, DJ;Curtis, JL
凋亡细胞必须清除以消除炎症，但很少有来自正常肺的常驻肺泡巨噬细胞（AMo）摄取凋亡细胞。我们研究了在引物C57BL/6小鼠气管内刺激引起的免疫炎症期间，凋亡细胞的Mo摄入是如何改变的。在静脉注射PKH26激发前，原位标记常驻AMo，以区分它们与募集的单核细胞。利用流式细胞术，我们在体外和体内鉴定了荧光标记的凋亡胸腺细胞被肺泡单核吞噬，并测量了表面分子的表达。气管内刺激诱导单核细胞快速募集，在第3天达到峰值，随后减少，而常驻AMo的数量没有显著变化。在任何时候，吞噬细胞在体外摄取凋亡胸腺细胞的比例在常驻的AMo中（28-45%）都高于招募的单核细胞（9-19%），但这两种细胞类型相对于摄取免疫球蛋白活化的靶标而言都较低。体内单核细胞的摄取量也有不显著的下降趋势。MerTK，一种对凋亡细胞吞噬至关重要的受体酪氨酸激酶，由常驻的AMo表达，而不是由募集的单核细胞表达。相对于常驻AMo，募集到肺泡的单核细胞摄取凋亡细胞较少，可能是由于缺乏MerTK表达。
Apoptotic cells must be cleared to resolve inflammation, but few resident alveolar macrophages (AMo) from normal lungs ingest apoptotic cells. We examined how Mo ingestion of apoptotic cells is altered during immune inflammation induced by intratracheal challenge of primed C57BL/6 mice using sheep red blood cells. Resident AMo were labeled in situ before challenge using intravenous PKH26 to distinguish them from recruited monocytes. Using flow cytometry, we identified phagocytosis of fluorescently-labeled apoptotic thymocytes by alveolar mononuclear phagocytes in vitro and in vivo, and measured surface molecule expression. Intratracheal challenge induced rapid recruitment of monocytes, peaking at Day 3 and decreasing thereafter, whereas numbers of resident AMo did not change significantly. At all times, the percentage of phagocytes ingesting apoptotic thymocytes in vitro was greater among resident AMo (28-45%) than among recruited monocytes (9-19%), but, was low in both cell types relative to ingestion of immunoglobulin-opsonized targets. There was also a nonsignificant trend toward lower ingestion by monocytes in vivo. MerTK, a receptor tyrosine kinase crucial for apoptotic cell phagocytosis, was expressed by resident AMo, but not by recruited monocytes. Relative to resident AMo, monocytes recruited to the alveolus ingest apoptotic cells meagerly, possibly due to absence of MerTK expression.