Alveolar Epithelial Cells Are Critical in Protection of the Respiratory Tract by Secretion of Factors Able To Modulate the Activity of Pulmonary Macrophages and Directly Control Bacterial Growth
Alveolar Epithelial Cells Are Critical in Protection of the Respiratory Tract by Secretion of Factors Able To Modulate the Activity of Pulmonary Macrophages and Directly Control Bacterial Growth
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DOI：
10.1128/iai.00950-12
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发表时间：
2013-01-01
影响因子：
3.1
通讯作者：
Fernandez, Carmen
中科院分区：
文献类型：
--
作者：
Chuquimia, Olga D.;Petursdottir, Dagbjort H.;Fernandez, Carmen
呼吸道上皮是一种物理和功能性屏障，积极参与环境因子的清除。肺泡隔室内衬有被称为I型肺泡上皮细胞（AEC I）的膜性肺细胞和被称为II型肺泡上皮细胞（AEC II）的颗粒性肺细胞。AEC II负责损伤后的上皮修复和离子转运，并且在免疫学上非常活跃，通过分泌抗微生物因子而有助于肺防御。AEC II还分泌多种因子，如细胞因子和趋化因子，参与免疫细胞的活化和分化，并能够将抗原呈递给特异性T细胞。另一种在肺防御中重要的细胞类型是肺巨噬细胞（PuM）。考虑到肺泡的结构，外部和内部隔室之间的良好沟通对于建立有效的反应至关重要。我们的假设是，在界面，AEC可能在从外部到内部的隔室的信号传递和在调节PuM的活动中发挥重要作用。为此，我们收集了来自未刺激或在体外用脂多糖（LPS）刺激的AEC的上清液。在各种设置中使用这些AEC条件培养基以测试对许多巨噬细胞功能的影响：（i）迁移，（ii）细菌生长的吞噬作用和细胞内控制，以及（iii）表型变化和形态。最后，我们测试了AEC条件培养基对细菌生长的直接影响。我们发现AEC分泌的因子具有双重作用，一方面控制细菌生长，另一方面增加巨噬细胞活性。
The respiratory epithelium is a physical and functional barrier actively involved in the clearance of environmental agents. The alveolar compartment is lined with membranous pneumocytes, known as type I alveolar epithelial cells (AEC I), and granular pneumocytes, type II alveolar epithelial cells (AEC II). AEC II are responsible for epithelial reparation upon injury and ion transport and are very active immunologically, contributing to lung defense by secreting antimicrobial factors. AEC II also secrete a broad variety of factors, such as cytokines and chemokines, involved in activation and differentiation of immune cells and are able to present antigen to specific T cells. Another cell type important in lung defense is the pulmonary macrophage (PuM). Considering the architecture of the alveoli, a good communication between the external and the internal compartments is crucial to mount effective responses. Our hypothesis is that being in the interface, AEC may play an important role in transmitting signals from the external to the internal compartment and in modulating the activity of PuM. For this, we collected supernatants from AEC unstimulated or stimulated in vitro with lipopolysaccharide (LPS). These AEC-conditioned media were used in various setups to test for the effects on a number of macrophage functions: (i) migration, (ii) phagocytosis and intracellular control of bacterial growth, and (iii) phenotypic changes and morphology. Finally, we tested the direct effect of AEC-conditioned media on bacterial growth. We found that AEC-secreted factors had a dual effect, on one hand controlling bacterial growth and on the other hand increasing macrophage activity.