Regulation of macrophage cytokine production by phagocytosis of apoptotic and post-apoptotic cells
Regulation of macrophage cytokine production by phagocytosis of apoptotic and post-apoptotic cells
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DOI：
10.1042/bst0260653
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发表时间：
1998-11-01
影响因子：
3.9
通讯作者：
Henson, PM
中科院分区：
文献类型：
--
作者：
Fadok, VA;McDonald, PP;Henson, PM
识别和清除是大多数凋亡细胞在体内生命中最后的共同事件。巨噬细胞在这项任务中特别有天赋，因此在炎症的解决中起着核心作用。由于巨噬细胞在凋亡细胞溶解之前就将其清除，因此阻止了潜在毒性和/或促炎细胞内内容物的释放。然而，摄取凋亡细胞比简单地去除有害物质有更复杂的好处。Meagher等人和Stern等人的研究表明，人单核细胞来源的巨噬细胞摄取凋亡的中性粒细胞或嗜酸性粒细胞不会诱导粒细胞巨噬细胞集落刺激因子（GM-CSF）或血栓素B2的分泌[1,2]。这与坏死细胞或调理细胞形成鲜明对比，这两种细胞都是诱导的。我们随后发现，凋亡细胞实际上通过包括转化生长因子（TGF） P[3]在内的自分泌/旁分泌机制，抑制了脂多糖（LPS）或酶聚糖刺激巨噬细胞产生的许多促炎细胞因子。发现凋亡细胞摄取抑制GM-CSF、白细胞介素(IL)-lP、IL-8、IL-10和肿瘤坏死因子（TNF） a的产生。与其他细胞因子相比，TGFP水平升高。通过在抗TGFP抗体存在下共孵育LPS、巨噬细胞和凋亡细胞，我们能够逆转其他细胞因子的抑制，这表明TGFP的自分泌产生是我们观察到的细胞因子抑制的部分原因。在这些研究中，我们使用的巨噬细胞主要利用qP3和CD36来识别凋亡细胞；磷脂酰丝氨酸脂质体或水溶性磷脂酰丝氨酸类似物均不抑制巨噬细胞对凋亡细胞的摄取。因此，我们继续检查
Recognition and removal is the final common event in the lives of most apoptotic cells in vivo. Macrophages are particularly talented at this task and therefore play a central role in the resolution of inflammation. Because macrophages remove apoptotic cells prior to their lysis, the release of potentially toxic and/or pro-inflammatory intracellular contents is prevented. Uptake of apoptotic cells has more complex benefits than simple removal of noxious substances, however. It was shown by Meagher et al. and then by Stern et al. that uptake of apoptotic neutrophils or eosinophils by human monocyte-derived macrophages did not induce secretion of granulocytemacrophage colony stimulating factor (GM-CSF) or thromboxane B2 [1, 2]. This was in marked contrast with necrotic or opsonized cells, which induced both. We subsequently found that apoptotic cells actually inhibited the production of many pro-inflammatory cytokines by macrophages stimulated with either lipopolysaccharide (LPS) or zymosan through an autocrine/paracrine mechanism involving transforming growth factor (TGF) P [3]. Apoptotic cell uptake was found to suppress production of GM-CSF, interleukin (IL)-lP, IL-8, IL-10, and tumour necrosis factor (TNF) a. In contrast with the other cytokines, TGFP levels were increased. By co-incubating LPS, macrophages, and apoptotic cells in the presence of anti-TGFP antibodies, we were able to reverse the suppression of the other cytokines, suggesting that the autocrine production of TGFP was responsible, in part, for the cytokine inhibition we observed. In these studies, we used macrophages which utilized primarily qP3 and CD36 by which to recognize apoptotic cells; uptake of apoptotic cells by these macrophages was not inhibited by phosphatidylserine (PS) liposomes or by water-soluble PS analogues. We therefore went on to examine the