Localization of inducible nitric oxide synthase and endothelial constitutive nitric oxide synthase in airway mucosa of toluene diisocyanate-induced asthma.
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.
Lee
Soo-Keol
SK
Department of Allergy and Rheumatology, Ajou University School of Medicine, Paldalgu Wonchondong San-5, Suwon 442-721, Korea.
Park
Hae-Sim
HS
Lim
Hyun-ee
HE
Kim
Sun-Sin
SS
Nahm
Dong-Ho
DH
Lee
Young-Mok
YM
Park
Choon-Sik
CS
D000328:Adult; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology*; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D020545:Respiratory Mucosa / Q000201:enzymology*; D014051:Toluene 2,4-Diisocyanate
D007074:Immunoglobulin G; D014051:Toluene 2,4-Diisocyanate; D009569:Nitric Oxide; D007073:Immunoglobulin E; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III