Localization of inducible nitric oxide synthase and endothelial constitutive nitric oxide synthase in airway mucosa of toluene diisocyanate-induced asthma.

Abstract

Endogenous exhaled nitric oxide (NO) is increased in asthma patients, especially in the exacerbated state. To evaluate the role of NO in airway mucosa of toluene diisocyanate (TDI)-induced asthma in relation to clinical and immunologic findings, 20 TDI-induced asthma patients were enrolled and classified into two groups: 9 newly diagnosed patients (group I) and 11 patients having persistent asthma symptoms for > 5 years despite work withdrawal (group II). Immunohistocytochemistry was applied to compare the expression of endothelial constitutive NOS (c-NOS) and induced NOS (i-NOS) in airway mucosa of both groups. They were observed in four areas: epithelium (EP), smooth muscle (SM), vascular endothelium (VE), and mucous gland (MG). The intensity of expression was graded on a scale of one to four and mean values were presented from blind readings observed by two experts. Serum-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) antibodies to TDI-human serum albumin conjugate were measured by enzyme-linked immunosorbent assay. e-NOS was found most frequently in VE (5/6 [83.3] versus 7/10 [70%]) followed by MG, EP, and SM in both groups, i-NOS was found most frequently in EP (7/9 [77.8%] versus 7/11 [63.6%]), followed by MG, VE, and SM in both groups. The intensities of i-NOS and c-NOS of MG were significantly higher in group I than in group II (p < 0.05) with no significant differences in other areas (p > 0.05, respectively). There were no significant correlations between i-NOS or c-NOS expression and exposure or asthma symptom duration (p > 0.05). No associations were found between i-NOS or c-NOS expression and the presence of specific IgE or IgG to TDI-human serum albumin conjugate (p > 0.05, respectively). In conclusion, i-NOS and c-NOS expressions were noted in EP, SM, VE, and MG in airway mucosa of TDI-induced asthma patients, which may contribute to airway inflammation.