在基线时可在人支气管肺泡灌洗液中检测到溶血磷脂酸，在节段性变应原激发后其水平升高。

Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge.

作者信息

Georas S N, Berdyshev E, Hubbard W, Gorshkova I A, Usatyuk P V, Saatian B, Myers A C, Williams M A, Xiao H Q, Liu M, Natarajan V

机构信息

Division of Pulmonary & Critical Care Medicine, The Johns Hopkins Asthma & Allergy Center, Baltimore, MD, USA.

出版信息

Clin Exp Allergy. 2007 Mar;37(3):311-22. doi: 10.1111/j.1365-2222.2006.02626.x.

DOI:10.1111/j.1365-2222.2006.02626.x

PMID:17359381

Abstract

BACKGROUND

Lysophosphatidic acid (LPA) is a biologically active lysophospholipid and a component of normal plasma. LPA binds to receptors expressed on circulating and structural lung cells and affects cell growth and activation. Whether LPA is present in the lung has not been previously reported.

OBJECTIVE

To develop an assay to measure LPA in bronchoalveolar lavage (BAL) fluids, and to study the association between LPA and allergic airway inflammation.

METHODS

Seventeen allergic subjects underwent bronchoscopy and segmental allergen challenge, followed 18 h later by BAL. Supernatants were analysed for LPA content using liquid chromatography and mass spectroscopy. Expression of LPA receptors on primary bronchial epithelial cells was analysed by immunolabelling, and the effects of LPA on epithelial cell barrier function was investigated by measuring transepithelial resistance.

RESULTS

LPA was detectable in BAL from control lung segments, and significantly increased 18 h after allergen challenge. Polyunsaturated species of LPA were especially increased following segmental allergen challenge. LPA levels did not strongly correlate with the number or percentages of eosinophils, neutrophils of lymphocytes, whereas MIP-3alpha (CCL20) levels correlated significantly with the allergen-driven influx of lymphocytes. The levels of LPA from control sites correlated inversely with BAL protein content, suggesting that LPA promoted epithelial barrier integrity at baseline. Experiments using primary human bronchial epithelial cells confirmed that LPA tightened the epithelial cell barrier.

CONCLUSION

Lysophosphatidic acid is detectable in human BAL fluids at baseline and its expression increases during allergic inflammation. LPA does not appear to be a dominant chemoattractant for eosinophils or lymphocytes during allergic airway inflammation. In the absence of ongoing inflammation, LPA may promote epithelial barrier integrity.

摘要

背景

溶血磷脂酸（LPA）是一种具有生物活性的溶血磷脂，是正常血浆的组成成分。LPA与循环系统及肺组织结构性细胞上表达的受体结合，影响细胞生长和激活。此前尚无关于LPA是否存在于肺组织中的报道。

目的

建立一种检测支气管肺泡灌洗（BAL）液中LPA的方法，并研究LPA与变应性气道炎症之间的关联。

方法

17名变应性受试者接受支气管镜检查及节段性变应原激发试验，18小时后进行BAL。采用液相色谱和质谱分析法分析上清液中的LPA含量。通过免疫标记分析原代支气管上皮细胞上LPA受体的表达，并通过测量跨上皮电阻研究LPA对上皮细胞屏障功能的影响。

结果

在对照肺段的BAL液中可检测到LPA，变应原激发试验18小时后LPA显著增加。节段性变应原激发试验后，多不饱和LPA种类尤其增加。LPA水平与嗜酸性粒细胞、中性粒细胞或淋巴细胞的数量或百分比无强相关性，而MIP-3α（CCL20）水平与变应原驱动的淋巴细胞流入显著相关。对照部位的LPA水平与BAL液蛋白含量呈负相关，提示LPA在基线时促进上皮屏障完整性。使用原代人支气管上皮细胞进行的实验证实LPA可收紧上皮细胞屏障。