Lack of IL-10 synthesis by murine alveolar macrophages upon lipopolysaccharide exposure.: Comparison with peritoneal macrophages
Lack of IL-10 synthesis by murine alveolar macrophages upon lipopolysaccharide exposure.: Comparison with peritoneal macrophages
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DOI：
10.1002/jlb.67.4.545
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发表时间：
2000-04-01
影响因子：
5.5
通讯作者：
Chignard, M
中科院分区：
文献类型：
--
作者：
Salez, L;Singer, M;Chignard, M
肺泡巨噬细胞在脂多糖（LPS）诱导的肺部炎症的建立中的中心作用已得到充分证实。它们产生并释放许多促炎分子，其中包括肿瘤坏死因子α（TNF-α），一种部分导致嗜酸性肺泡炎的细胞因子。由LPS激活的单核吞噬细胞产生的白细胞介素-10（IL-10）是下调TNF-α合成的主要抗炎细胞因子。我们研究了小鼠肺泡巨噬细胞在体内和体外对LPS产生IL-10的能力，出乎意料的是，LPS鼻内滴注后，在整个肺和空气中均未检测到IL-10蛋白。此外，在分离的和LPS刺激的肺泡巨噬细胞上清液中也未检测到IL-10蛋白，通过不存在特异性RNA转录物证实了IL-10合成的缺乏。相比之下，正如预期的那样，自体腹膜巨噬细胞在LPS攻击后产生IL-10。通常改变TNF-α/IL-10平衡以有利于IL-10的药物被使用，但没有成功。因此，允许细胞内cAMP浓度增加的操作不能逆转这种意想不到的表型。此外，与腹膜巨噬细胞相比，用PMA直接激活蛋白激酶C不能触发肺泡巨噬细胞形成IL-10，目前的研究结果描述了小鼠肺泡巨噬细胞在LPS诱导的炎症过程中的特定表型。
The central role of alveolar macrophages in the establishment of lipopolysaccharide (LPS)-induced lung inflammation is well demonstrated. They produce and release numerous proinflammatory molecules, among which is tumor necrosis factor alpha (TNF-alpha), a cytokine responsible in part for the neutrophilic alveolitis. Interleukin-10 (IL-10) produced by LPS-activated mononuclear phagocytes is a major anti-inflammatory cytokine that down-regulates TNF-alpha synthesis. We studied the ability of murine alveolar macrophages to produce IL-10 in vivo and in vitro, in response to LPS, Unexpectedly, the IL-10 protein was not detected in the whole lung and airspaces after LPS intranasal instillation, In addition, no IL-10 protein was found in supernatants of isolated and LPS-stimulated alveolar macrophages, The lack of IL-10 synthesis was confirmed by the absence of specific RNA transcripts, By contrast and as expected, autologous peritoneal macrophages produced IL-10 upon LPS challenge. Drugs that usually modify the TNF-alpha/IL-10 balance in favor of IL-10 were used without success, Thus, maneuvers allowing an increase in intracellular cAMP concentrations did not reverse this unexpected phenotype, Moreover, direct activation of protein kinase C with PMA was unable to trigger IL-10 formation by alveolar, by contrast to peritoneal, macrophages, The current findings describe a specific phenotype for murine alveolar macrophages during LPS-induced inflammation.