Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor.
Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor.
复制标题
通过粒细胞/巨噬细胞刺激因子抑制居民肺肺泡巨噬细胞的免疫抑制活性。
DOI：
10.1084/jem.177.6.1773
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发表时间：
1993-06-01
影响因子：
15.3
通讯作者：
Holt, P G
中科院分区：
文献类型：
--
作者：
Bilyk, N;Holt, P G
肺泡巨噬细胞（PAM）通过下调局部T细胞的稳态应答，在维持肺内免疫稳态中发挥重要作用。本研究表明，这种T细胞抑制途径是可逆的，通过粒细胞/巨噬细胞集落刺激因子（GM-CSF）。因此，新鲜分离的PAM强烈抑制促分裂原诱导的T细胞增殖，并且用通过将肺暴露于细菌脂多糖（LPS）产生的富含精氨酸的肺条件培养基（LCM）预处理PAM消除了这种抑制活性。正常和无胸腺裸鼠肺LCM表现出相同的活性。此外，LCM的PAM调节活性可被GM-CSF特异性封闭抗体抑制，并且LCM的活性可被重组GM-CSF复制。这表明间充质细胞和/或巨噬细胞在诸如LPS的试剂的刺激下分泌GM-CSF提供了在急性炎症期间上调局部T细胞反应性的潜在机制。此外，一系列细胞因子的实验表明，白细胞介素4、转化生长因子β 1和肿瘤坏死因子α（TNF-α）对PAM的调节作用较弱（但显著），并且（在TNF-α的情况下）放大了GM-CSF的作用。
Resident pulmonary alveolar macrophages (PAM) play an important role in the maintenance of immunological homeostasis in the lung via downmodulation of local T cell responses in the steady state. The present study demonstrates that this pathway for T cell suppression is reversible via granulocyte/macrophage colony-stimulating factor (GM- CSF). Thus, freshly isolated PAM strongly inhibit mitogen-induced T cell proliferation, and pretreatment of the PAM with cytokine-rich lung- conditioned medium (LCM) generated by exposure of lung to bacterial lipopolysaccharide (LPS) abrogated this suppressive activity. LCM from lungs of normal and athymic nude mice exhibited identical activity. Moreover, the PAM-modulating activity of LCM was inhibited by blocking antibody specific for GM-CSF, and the activity of LCM could be reproduced by recombinant GM-CSF. This suggests that secretion of GM- CSF by mesenchymal cells and/or macrophages under stimulation from agents such as LPS provides a potential mechanism for upregulation of local T cell responsiveness during acute inflammation. In addition, experiments with a range of cytokines indicated that interleukin 4, transforming growth factor beta 1 and tumor necrosis factor alpha (TNF- alpha) exhibited weaker (but significant) modulatory effects on PAM, and (in the case of TNF-alpha) amplified the effects of GM-CSF.