Fibrocytes Contribute to Inflammation and Fibrosis in Chronic Hypersensitivity Pneumonitis through Paracrine Effects
Fibrocytes Contribute to Inflammation and Fibrosis in Chronic Hypersensitivity Pneumonitis through Paracrine Effects
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DOI：
10.1164/rccm.201407-1334oc
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发表时间：
2015-02-15
影响因子：
24.7
通讯作者：
Selman, Moises
中科院分区：
文献类型：
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作者：
de Alba, Carolina Garcia;Buendia-Roldan, Ivette;Selman, Moises
原理：超敏性肺炎（HP）是一种由暴露于多种抗原引起的肺部炎症。慢性HP可演变为肺纤维化。目的：探讨慢性HP中纤维细胞的作用。方法：采用流式细胞术检测CD 45（+）/CXCR 4（+）/Col-I+循环中纤维细胞，采用共聚焦显微镜观察HP和正常肺组织中纤维细胞的存在。通过ELISA定量血浆和支气管肺泡灌洗液中CXCL 12的浓度。测量和主要结果：与健康个体相比，HP患者循环纤维细胞的百分比显着增加（5.3 +/- 3.4%对0.8 +/- 0.7%; P = 0.00004）。HP肺内纤维母细胞和淋巴细胞附近可见大量纤维细胞浸润。HP患者血浆CXCL 12浓度显著升高（2，303.3 +/- 813.7 vs. 1，385.6 +/- 318.5 pg/ml; P=0.00003），支气管肺泡灌洗液中也发现类似结果。趋化因子主要由上皮细胞表达。在共培养中，纤维细胞诱导肺成纤维细胞α（1）I型胶原蛋白，基质金属蛋白酶-1和血小板衍生生长因子-β的表达显着增加。同样，纤维细胞诱导的上调CCL 2在HP淋巴细胞和fibroblasts.Conclusions：这些研究结果表明，高水平的纤维细胞存在于慢性HP患者的外周血中，这些细胞浸润HP肺。纤维细胞可能参与HP的发病机制，通过旁分泌信号诱导多种促炎和促纤维化分子的分泌来放大炎症和纤维化反应。
Rationale: Hypersensitivity pneumonitis (HP) represents a lung inflammation provoked by exposure to a variety of antigens. Chronic HP may evolve to lung fibrosis. Bone marrow derived fibrocytes migrate to injured tissues and contribute to fibrogenesis, but their role in HP is unknown.Objectives: To assess the possible participation of fibrocytes in chronic HP.Methods: CD45(+)/CXCR4(+)/Col-I+ circulating fibrocytes were evaluated by flow cytometry, and the presence of fibrocytes in HP and normal lungs by confocal microscopy. The concentration of CXCL12 in plasma and bronchoalveolar lavage fluids was quantified by ELISA. The effect of fibrocytes on lung fibroblasts and T lymphocytes was examined in co-cultures.Measurements and Main Results: The percentage of circulating fibrocytes was significantly increased in patients with HP compared with healthy individuals (5.3 +/- 3.4% vs. 0.8 +/- 0.7%; P = 0.00004). Numerous fibrocytes were found infiltrating the HP lungs near fibroblasts and lymphocytes. Plasma CXCL12 concentration was significantly increased in patients with HP (2,303.3 +/- 813.7 vs. 1,385.6 +/- 318.5 pg/ml; P=0.00003), and similar results were found in bronchoalveolar lavage fluids. The chemokine was primarily expressed by epithelial cells. In co-cultures, fibrocytes induced on lung fibroblasts a significant increase in the expression of alpha(1) type I collagen, matrix metalloprotease-1, and platelet-derived growth factor-beta. Likewise, fibrocytes induced the up-regulation of CCL2 in HP lymphocytes and fibroblasts.Conclusions: These findings demonstrate that high levels of fibrocytes are present in the peripheral blood of patients with chronic HP and that these cells infiltrate the HP lungs. Fibrocytes may participate in the pathogenesis of HP, amplifying the inflammatory and fibrotic response by paracrine signaling inducing the secretion of a variety of proinflammatory and profibrotic molecules.