Plasminogen Activator Inhibitor-1 Plasma Concentration in Allergic Asthma Patients during Allergen Challenge

Abstract

Background: The –675 4G/5G plasminogen activator inhibitor-1 (PAI-1) polymorphism is linked with asthma and bronchial hyperreactivity. The aim of this study was to evaluate the effect of allergen challenge on plasma PAI-1 concentration in relation to the –675 4G/5G PAI-1 gene polymorphism in house dust mite-allergic asthma patients (HDM-AAs). Materials and Methods: The study was performed in 54 HDM-AAs and 54 healthy nonatopic controls (HCs). Plasma samples were collected in HDM-AAs before, as well as 30 min, 6 h and 24 h after allergen challenge and at corresponding time points in sham-challenged HCs. Results: In subjects carrying the individual PAI-1 genotype, the mean baseline plasma PAI-1 concentration was greater in HDM-AAs than in HCs. At 30 min the mean increase in plasma PAI-1 concentration was significantly greater in HDM-AAs (14.4 ± 12.9 ng/ml) than in HCs (3.4 ± 3.2 ng/ml; p < 0.001). At 6 h, plasma PAI-1 concentration greater than before challenge was found in only 4 HCs (7.4%) but in 48 HDM-AAs (88.9%; p < 0.0001). An increase in plasma PAI-1 concentration at 6 h was found in all HDM-AAs carrying the 4G allele but only in 33.3% of the 5G homozygotes (p < 0.0001). The strongest correlation was found between log PC₂₀ and PAI-1 plasma concentration over the period of 24 h (r = –0.507; p = 0.0001). Conclusion: Changes in plasma PAI-1 concentration associated with allergen-induced bronchoconstriction are modulated by the –675 4G/5G polymorphism of the PAI-1 gene. Allergen-induced upregulation of PAI-1 synthesis may participate in the development of bronchial hyperreactivity in HDM-AAs.

Plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in sputum of allergic asthma patients.

“…We have been already able to demonstrate that in asthmatic patients plasma PAI-1 concentration correlates with baseline FEV 1 and bronchial response to histamine, but it does not correlate with peripheral blood eosinophilia or response to allergen challenge [15,22]. Moreover, in asthmatic patients the -675 4G allele of PAI-1 gene, which is a major genetic determinant of increased PAI-1 synthesis, is associated with lower baseline lung function and greater bronchial reactivity to histamine, suggesting that propensity for increased PAI-1 production is linked with bronchial remodeling [15].…”

“…Moreover, in asthmatic patients the -675 4G allele of PAI-1 gene, which is a major genetic determinant of increased PAI-1 synthesis, is associated with lower baseline lung function and greater bronchial reactivity to histamine, suggesting that propensity for increased PAI-1 production is linked with bronchial remodeling [15]. Furthermore, exposure to an allergen, which leads to increased non-specific bronchial reactivity, induces PAI-1 synthesis [22]. However, no direct correlation between the increase in plasma PAI PAI-1 level and indices of airway inflammation in allergic asthmatic patients.…”

“…Concentration of PAI-1 and uPA antigen in the supernatants was evaluated using enzymelinked immunosorbent assays (Asserachrom, Diagnostica Stago, USA) according to the manufacturer's instruction as described before [22]. All samples were run in duplicates.…”

Concentrations of plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in induced sputum of asthma patients after allergen challenge.

“…Allergen exposure is associated with increased plasma PAI-1 concentration [17]. Plasma exudate from microvascular leakage during asthmatic response may lead to efflux of PAI-1 into airways.…”

“…In clinically stable, mild allergic asthma patients elevated levels of uPA and PAI-1 in induced sputum have recently been demonstrated [16]. Moreover, allergen exposure leads to elevation of plasma PAI-1 concentration in allergic asthma patients [17]. It is not known wheather allergen exposure leads also to local (intrabronchial) upregulation of PAI-1 expression promoting in this way airway remodeling.…”