Kowal Krzysztof, Moniuszko Marcin, Zukowski Sebastian, Bodzenta-Lukaszyk Anna
Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
Folia Histochem Cytobiol. 2010 Dec;48(4):518-23. doi: 10.2478/v10042-010-0075-2.
Urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) are involved in tiisue remodeling and repair processes associated with acute and chronic inflammation. The aim of the study was to evaluate the effect of allergen challenge on concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs). Thirty HDM-AAs and ten healthy persons (HCs)were recruited for the study. In 24 HDM-AAs bronchial challenge with Dermatophagoides pteronyssinus (Dp) and in 6 HDM-AAs sham challenege with saline were performed. In HDM-AAs sputum was induced 24 hours before (T0) and 24 hours (T24) after the challenge. Concentration of uPA and PAI-1 in induced sputum were determined using immunoenzymatic assays. At T0 in HDM-AAs mean sputum uPA (151 ± 96 pg/ml) and PAI-1 (4341 ± 1262 pg/ml) concentrations were higher than in HC (18.8 ± 6.7 pg/ml; p=0.0002 and 596 ± 180 pg/ml; p<0.0001; for uPA and PAI-1 respectively). After allergen challenge further increase in sputum uPA (187 ± 144 pg/ml; p=0.03) and PAI-1 (6252 ± 2323 pg/ml; p<0.0001) concentrations were observed. Moreover, in Dp challenged, but not in saline challenged HDM-AAs the mean uPA/PAI-1 ratio decreased significantly at T24. No significant increase in the studied parameters were found in sham challenged patients. In HDM-AAs allergen exposure leads to activation of the plasmin system in the airways. Greater increase of the PAI-1 concentration than uPA concentration after allergen challenge may promote airway remodeling and play an important role in the development of bronchial hyperreactivity.
尿激酶型纤溶酶原激活剂(uPA)及其抑制剂(PAI-1)参与了与急慢性炎症相关的组织重塑和修复过程。本研究的目的是评估变应原激发对屋尘螨过敏性哮喘患者(HDM-AAs)诱导痰中uPA和PAI-1浓度的影响。本研究招募了30名HDM-AAs患者和10名健康人(HCs)。对24名HDM-AAs患者进行了支气管激发试验,用尘螨(Dp)进行激发,对6名HDM-AAs患者用生理盐水进行假激发试验。在HDM-AAs患者中,于激发前24小时(T0)和激发后24小时(T24)诱导痰液。采用免疫酶法测定诱导痰中uPA和PAI-1的浓度。在T0时,HDM-AAs患者痰液中uPA的平均浓度(151±96 pg/ml)和PAI-1的平均浓度(4341±1262 pg/ml)高于HCs(分别为18.8±6.7 pg/ml;p=0.0002和596±180 pg/ml;p<0.0001,uPA和PAI-1)。变应原激发后,痰液中uPA(187±144 pg/ml;p=0.03)和PAI-1(6252±2323 pg/ml;p<0.0001)的浓度进一步升高。此外,在Dp激发的HDM-AAs患者中,但在生理盐水激发的HDM-AAs患者中未观察到,T24时uPA/PAI-1平均比值显著降低。在假激发试验的患者中,未发现所研究参数有显著增加。在HDM-AAs患者中,变应原暴露导致气道中纤溶酶系统激活。变应原激发后PAI-1浓度的升高幅度大于uPA浓度,这可能促进气道重塑,并在支气管高反应性的发展中起重要作用。