纤维细胞定位于气道平滑肌是哮喘的特点
2009/02/24
背景：气道平滑肌(ASM)增生是哮喘的一个标志，与疾病严重程度和持续的气道阻塞有关。
目标：研究在哮喘患者的气道平滑肌中，作为外周血骨髓祖细胞之一的纤维细胞是否增多。
方法：我们评估了轻－重度难治性哮喘患者气道活检标本和外周血中成纤维细胞的数量，同时通过体外实验，探讨了调控纤维细胞向气道平滑肌移行的可能机制。
结果：对51名哮喘受试者和33个对照人群进行研究。与健康对照组(均值[四分位数]，0/mm2 [0.3/mm2])相比，重度难治性哮喘患者支气管粘膜固有层的纤维细胞数目(1.9/mm2 [1.7/mm2]，P < 0.0001)和所有炎症程度哮喘患者平滑肌束成纤维细胞数目(重症哮喘，3.8/mm2 [9.4/mm2]、轻至中度哮喘，1.1/mm2 [2.4/mm2])高于对照组(0/mm2 [0/mm2]; P = 0.0004)均明显增加；重度难治性哮喘患者外周血中的纤维细胞数量(1.4 × 104/mL [2.6 × 104/ml)]也明显高于健康对照组(0.4 × 104/mL [1.0 × 104/mL], P =0.002)。我们发现，在体外ASM可促进纤维细胞的趋化和激活(迁移4.5小时后的距离，31μm [ 2.9μm]对17μm [ 2.4μm]，P＝0.001)，该作用部分是由血小板来源的生长因子PDGF介导 (中和抗体平均抑制率，16％ [ 95％可信区间，2-32％]，P＝0.03)，而不是通过激活趋化因子受体。
结论：该研究首次证明：在哮喘中，成纤维细胞存在于哮喘患者气道平滑肌间隔，并可以促进纤维细胞迁移。成纤维细胞在哮喘患者气道平滑肌增生及气道功能障碍过程的所起的作用仍有待研究。
（陈欣 审校）
Saunders R, et al. J Allergy Clin Immunol. 2008 Dec 9. [Epub ahead of print]
Fibrocyte localization to the airway smooth muscle is a feature of asthma.
Saunders R, Siddiqui S, Kaur D, Doe C, Sutcliffe A, Hollins F, Bradding P, Wardlaw A, Brightling CE.
Institute for Lung Health, Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
BACKGROUND: Airway smooth muscle (ASM) hyperplasia is a hallmark of asthma that is associated with disease severity and persistent airflow obstruction.
OBJECTIVES: We sought to investigate whether fibrocytes, a population of peripheral blood mesenchymal progenitors, are recruited to the ASM compartment in asthma.
METHODS: We assessed the number of fibrocytes in bronchial biopsy specimens and peripheral blood from subjects with mild-to-severe refractory asthma versus healthy control subjects. In vitro we investigated potential mechanisms controlling fibrocyte migration toward the ASM bundle.
RESULTS: Fifty-one subjects with asthma and 33 control subjects were studied. In bronchial biopsy specimens, the number of fibrocytes was increased in the lamina propria of subjects with severe refractory asthma (median [interquartile range] number, 1.9/mm(2) [1.7/mm(2)]) versus healthy control subjects (median [interquartile range] number, 0/mm(2) [0.3/mm(2)], P < .0001) and in the ASM bundle of subjects with asthma of all severities (subjects with severe asthma, median [interquartile range] number, 3.8/mm(2) [9.4/mm(2)]; subjects with mild-to-moderate asthma, median [interquartile range] number, 1.1/mm(2) [2.4/mm(2)]); healthy control subjects, (median [interquartile range] number, 0/mm(2) [0/mm(2)]); P = .0004). In the peripheral blood the fibrocyte number was also increased in subjects with severe refractory asthma (median [interquartile range] number, 1.4 x 10(4)/mL [2.6 x 10(4)/mL]) versus healthy control subjects (median [interquartile range] number, 0.4 x 10(4)/mL [1.0 x 10(4)/mL], P = .002). We identified that in vitro ASM promotes fibrocyte chemotaxis and chemokinesis (distance of migration after 4.5 hours, 31 mum [2.9 mum] vs 17 mum [2.4 mum], P = .0001), which was in part mediated by platelet-derived growth factor (mean inhibition by neutralizing antibody, 16% [95% CI, 2% to 32%], P = .03) but not by activation of chemokine receptors.
CONCLUSION: This study provides the first evidence that fibrocytes are present in the ASM compartment in asthma and that ASM can augment fibrocyte migration. The importance of fibrocytes in the development of ASM hyperplasia and airway dysfunction in asthma remains to be determined.
