Plasminogen activator inhibitor-1 plasma concentration in allergic asthma patients during allergen challenge.
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).


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).


CONCLUSIONS
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.
Kowal
Krzysztof
K
Department of Allergology and Internal Medicines, Medical University of Bialystok, Bialystok, Poland. kowalkmd@yahoo.pl
Bodzenta-Lukaszyk
Anna
A
Pampuch
Agnieszka
A
Szmitkowski
Maciej
M
Donati
Maria Benedetta
MB
Iacoviello
Licia
L
D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000097:blood* / Q000276:immunology; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D011110:Polymorphism, Genetic
D000485:Allergens; D039741:Antigens, Dermatophagoides; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human