成纤维细胞通过旁分泌作用促进慢性变应性肺炎的炎症和纤维化。

Fibrocytes contribute to inflammation and fibrosis in chronic hypersensitivity pneumonitis through paracrine effects.

机构信息

1 Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico; and.

出版信息

Am J Respir Crit Care Med. 2015 Feb 15;191(4):427-36. doi: 10.1164/rccm.201407-1334OC.

DOI:10.1164/rccm.201407-1334OC

PMID:25531246

Abstract

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 α1 type I collagen, matrix metalloprotease-1, and platelet-derived growth factor-β. 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.

摘要

背景

过敏性肺炎（HP）代表一种由多种抗原暴露引起的肺部炎症。慢性 HP 可能进展为肺纤维化。骨髓来源的成纤维细胞向受损组织迁移，并有助于纤维化形成，但它们在 HP 中的作用尚不清楚。

目的

评估成纤维细胞在慢性 HP 中的可能参与作用。

方法

通过流式细胞术评估 CD45(+)/CXCR4(+)/Col-I(+)循环成纤维细胞，并通过共聚焦显微镜评估 HP 和正常肺中的成纤维细胞。通过 ELISA 定量血浆和支气管肺泡灌洗液中 CXCL12 的浓度。在共培养物中检查成纤维细胞对肺成纤维细胞和 T 淋巴细胞的影响。

测量和主要结果

与健康个体相比，HP 患者的循环成纤维细胞百分比显着增加（5.3±3.4%比 0.8±0.7%；P=0.00004）。在 HP 肺部的成纤维细胞和淋巴细胞附近发现了大量成纤维细胞浸润。HP 患者的血浆 CXCL12 浓度显着升高（2303.3±813.7 比 1385.6±318.5 pg/ml；P=0.00003），支气管肺泡灌洗液中也得到了类似的结果。趋化因子主要由上皮细胞表达。在共培养物中，成纤维细胞诱导肺成纤维细胞 α1 型 I 胶原、基质金属蛋白酶-1 和血小板衍生生长因子-β的表达显著增加。同样，成纤维细胞诱导 HP 淋巴细胞和成纤维细胞中 CCL2 的上调。