Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein kinase levels in nasal mucosae of antigen-challenged rats.

OBJECTIVE: In patients with severe allergic rhinitis, the most serious symptom is rhinostenosis, which is considered to be induced by a dilatation of plexus cavernosum. The vascular relaxing responses to chemical mediators are mainly mediated by the production of nitric oxide (NO). However, the exact mechanism(s) in nasal venoresponsiveness of allergic rhinitis is not fully understood. In the present study, we investigated the roles of soluble guanylate cyclase (sGC) and cyclic-guanosine monophosphate (c-GMP)-dependent protein kinase G (PKG) in venodilatation of nasal mucosae of antigen-challenged rats. METHODS: Actively sensitized rats were repeatedly challenged with aerosolized antigen (2,4-dinitrophenylated Ascaris suum). Twenty-four hours after the final antigen challenge, nasal septum mucosa was exposed surgically and observed directly in vivo under a stereoscopic microscope. The sodium nitroprusside (SNP) and 8-Br-cGMP (a PKG activator) were administered into arterial injection, and the venous diameters of nasal mucosa were observed. RESULTS: The intra-arterial injections of SNP and 8-Br-cGMP-induced venodilatation were significantly augmented in the nasal mucosae of repeatedly antigen-challenged rats. Furthermore, protein expressions of sGC and PKG were significantly increased in nasal mucosae of the antigen-challenged rats. CONCLUSION: The present findings suggest the idea that the promoted cGMP/PKG pathway may be involved in the enhanced NO-induced venodilatation in nasal mucosae of antigen-challenged rats.

Reduction in superoxide dismutase expression in the epithelial mucosa of eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Eosinophils generate large amounts of oxidant species. The eosinophil-dominant type of chronic rhinosinusitis (CRS) with nasal polyps is related to more extensive disease and a decreased likelihood of surgical success. Superoxide dismutase (SOD) is the first-line and only antioxidant enzyme that converts superoxide to hydrogen peroxide. METHODS: The patients with CRS with nasal polyps were divided into eosinophilic and noneosinophilic groups. The expression of three isoforms of SOD, intracellular copper-zinc SOD (CuZnSOD), mitochondrial manganese SOD (MnSOD) and extracellular SOD (ECSOD), were examined by enzyme activity assay, immunohistochemistry and quantitative real-time RT-PCR sampled by laser capture microdissection. RESULTS: SOD activity in the eosinophilic and noneosinophilic groups was significantly reduced compared to that of the control groups. Immunostaining of both CuZnSOD and MnSOD in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. CuZnSOD mRNA of the eosinophilic group was significantly decreased compared with that of the control group, whereas MnSOD mRNA in the eosinophilic group was significantly decreased compared with that in the noneosinophilic and control groups. Neither immunoreactivity nor mRNA of ECSOD was different among the three groups. The degree of epithelial damage and disease severity were inversely correlated with CuZnSOD and MnSOD immunoreactivity. CONCLUSIONS: The reduction in SOD activity and the downregulation of the SOD message are suggested to be related to eosinophil recruitment and epithelial damage of CRS with nasal polyps.

Macro-AST: misleading finding in an adolescent with MCAD-deficiency.

BACKGROUND: MCAD-deficiency is the most common inborn error of fatty acid oxidation now included in many newborn screening programms using MS/MS. During prolonged catabolic episodes, patients may suffer from metabolic decompensation with dysfunction of liver, skeletal- and heart muscle as well as brain. In anabolism, neither clinical symptoms nor biochemical signs of organ dysfunction occur. CASE PRESENTATION: We report a female patient with MCAD-deficiency in whom at the age of 11 years isolated AST-elevation was found without any clinical or biochemical signs of organ dysfunction. We showed by polyethylene glycol precipitation that macro-AST formation was responsible for this biochemical finding. AST was probably complexed with immunoglobulins possibly related to an allergic disposition. Macro-AST formation is not a special feature of MCAD-deficiency but rather a non-specific, coincidental finding which also occurs in healthy individuals. The general practitioner consulted by the patient before coming to our outpatient clinic for inborn errors of metabolism was worried that isolated AST-elevation indicated cell damage in MCAD-deficiency. He ordered further diagnostic tests like ultrasound, ECG and echocardiography without any pathology. CONCLUSION: In isolated AST-elevation, macro-AST has to be considered in order to avoid unnecessary, costly and invasive evaluation. This is not only true for healthy persons but for patients with chronic diseases like MCAD as well.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in nasal lavage after an inhalation challenge with flour.

OBJECTIVES/HYPOTHESIS: The existence of nasal mucosa remodeling in allergic rhinitis is controversial. Few data are available on the dynamics of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in nasal fluid after an allergen challenge. We examined whether an immediate allergic reaction that induces nasal congestion and inflammation is able to also induce changes in remodeling parameters in nasal fluid. STUDY DESIGN: Controlled experimental study. METHODS: Ten patients with allergic occupational rhinitis due to flour underwent a control and active inhalation challenge with serial monitoring of nasal congestion and nasal symptoms with acoustic rhinometry and a visual analogue scale. Levels of remodeling markers (MMP-2, MMP-7, MMP-9, MMP-13, TIMP-1, TIMP-2) and inflammatory cells in nasal fluid were measured before the challenge and at 30 minutes, 6 hours, and 24 hours following the challenge. RESULTS: In contrast to the control challenge, the flour challenge induced nasal symptoms and significant decreases in nasal volume in all subjects. After the flour challenge, a significant increase in nasal levels of TIMP-2 and a nonsignificant increase in TIMP-1 levels were observed, whereas no significant changes in nasal levels of MMPs were documented. CONCLUSIONS: This study showed that after an inhalation challenge with an occupational allergen, the nasal mucosa displayed an imbalance in favor of TIMPs enzymes activity as compared to MMPs enzymes activity, represented in an increase in nasal levels of TIMP-2 during the course of the early reaction following the allergen challenge.

Distinct effects of imperatorin on allergic rhinitis: imperatorin inhibits caspase-1 activity in vivo and in vitro.

Because imperatorin (IPT), the furanocoumarins exhibits anti-inflammatory activity, we reasoned that IPT might modulate the allergic rhinitis (AR). The aim of this study was to analyze the regulation of AR by IPT. Here, we show the effect and mechanism of IPT in an ovalbumin (OVA)-induced AR model. The number of rubs after the OVA challenge in the OVA-sensitized mice was significantly higher than that in the OVA-unsensitized mice. The increased number of rubs was inhibited by the oral administration of IPT. The increased levels of IgE and histamine in the OVA-sensitized mice were reduced by IPT administration. The levels of interferon-γ were enhanced, whereas the levels of interleukin (IL)-4 were reduced on the spleen tissue of the IPT-administered AR mice. Protein levels of IL-1ß, macrophage inflammatory protein-2, intercellular adhesion molecule-1, and cyclooxygenase-2 were reduced by IPT administration in the nasal mucosa of the OVA-sensitized mice. In the IPT-administered mice, the number of eosinophils and mast cells infiltration increased by OVA-sensitization were also decreased. In addition, IPT inhibited caspase-1 activity in the same nasal mucosa tissue. In activated human mast cells, the receptor-interacting protein 2 (RIP2), IκB kinase (IKK)-ß, nuclear factor-κB (NF-κB)/RelA, and caspase-1 activation were increased, but increased RIP2, IKK-ß, NF-κB/RelA, and caspase-1 activation were inhibited by the treatment of IPT. In addition, IPT inhibited caspase-1 activity and IL-1ß production in IgE-stimulated bone marrow-derived mast cells. We can conclude that IPT exerts significant effects by regulating of caspase-1 activation in AR animal and in vitro models.

Increased expression of arginase I and II in allergic nasal mucosa.

OBJECTIVES/HYPOTHESIS: It is known that arginase may be a regulator of diverse pathways, including production of nitric oxide (NO). Increased expression of arginase has been reported in several inflammatory lung diseases, including allergic asthma, suggesting that this may be a common feature underlying the pathophysiology of airway hyperreactivity. Thus, arginase I and II may play a role in the pathogenesis of allergic rhinitis. The distribution pattern and level of expression of arginase I and II were therefore determined in normal and allergic nasal mucosa. STUDY DESIGN: Controlled, prospective study. METHODS: The distribution pattern and level of expression of arginase I and II in normal and allergic nasal mucosa were evaluated using RT-PCR, immunohistochemistry, and Western blotting. RESULTS: The level of expression of arginase I and II mRNA was increased in allergic nasal mucosa in comparison with normal nasal mucosa. In normal nasal mucosa, arginase I and II were expressed in the surface epithelium, submucosal glands, vascular endothelium, and fibroblasts. In allergic nasal mucosa, both enzymes were also localized to similar sites, in addition to inflammatory cells, and the level of expression were greatly increased compared with normal nasal mucosa. These findings were verified by Western blotting. CONCLUSIONS: These results indicate that arginase I and II may play a role in the pathophysiology of allergic rhinitis, and suggest the possible role of the L-arginine metabolic pathway through modulation of L-arginine availability as a substrate for nitric oxide synthase (NOS) and arginase in the pathogenesis of allergic rhinitis.

Beneficial effects of chelidonic acid on a model of allergic rhinitis.

Chelidonic acid (CA) is known as an inhibitor of the rat brain glutamate decarboxylase. However, the pharmacological effects of CA in allergic reactions have not yet been defined. Here, we show the effects and the mechanism of CA in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model. CA significantly decreased the number of nasal/ear rubs and increment of IgE levels in the AR mice. The level of interferon-γ was enhanced while the level of IL-4 was reduced on the spleen tissue of the CA-administered AR mice. Expressions of IL-1ß and cyclooxygenase-2 were inhibited by CA administration in the nasal mucosa tissues. Infiltration of eosinophils and mast cells was decreased in the CA-administered AR mice. Furthermore, CA decreased the caspase-1 activity in the same nasal mucosa tissue and human mast cell line, HMC-1. Our results indicate that CA may attenuate allergic reaction by inhibition of caspase-1 activity.

Correlating matrix metalloproteinase-9 sinus secretion levels with tissue biopsy levels.

BACKGROUND: Collecting mucosal biopsies is invasive and creates additional inflammation, hampering a better understanding of nasal and sinus disease evolution and response to treatment. We examine whether sinus secretion collection can replace tissue biopsy for protein determination. METHODS: Prior to surgical intervention for chronic rhinosinusitis (CRS), a piece of gelatin foam was used to collect secretions from the ethmoid mucosa. A tissue biopsy was then taken from the same location. Matrix metalloproteinase-9 (MMP-9) protein levels were measured in each sample. RESULTS: MMP-9 protein levels in secretions and tissues were significantly correlated (p = 0.0033, r = 0.52, by Pearson correlation). CONCLUSION: Secretion collection can replace tissue biopsy for MMP-9 determinations, reducing morbidity. Furthermore, secretion collection allows sequential sampling from the same location.

Influence of desloratadine on selected oxidative stress markers in patients between 3 and 10 years of age with allergic perennial rhinitis.

The objective of this study was to evaluate the selected oxidative stress parameters in 50 (35 males, 15 females) pediatric patients aged from 3 to 10 years diagnosed with perennial allergic rhinitis before and after the two-month treatment with desloratadine at the dose of 5 mg/day and in 11 healthy individuals. Oxidative stress was determined by the analysis of the reactive oxygen species neutralizing enzyme activity in erythrocytes superoxide dismutase and catalase, the estimation of free radical processes intensity: content of malondialdehyde in erythrocytes and the level of plasma hydroperoxides as well as by quantification of the plasma total antioxidant status. Changes in the studied parameters in untreated perennial allergic rhinitis patients indicate increased oxidative stress. The treatment with desloratadine normalized the superoxide dismutase and catalase activity as well as the malondialdehyde formation. The plasma hydroperoxides level in treated patients with perennial allergic rhinitis is reduced as compared with untreated subjects, although still higher than in the control. Desloratadine caused an increase in the total antioxidant status level, but it was not statistically significant. It can be concluded that oxidative stress is implicated in the pathogenesis of perennial allergic rhinitis. The results demonstrate that desloratadine exerts antioxidant effects in vivo.

Overexpression of the superoxide anion and NADPH oxidase isoforms 1 and 4 (NOX1 and NOX4) in allergic nasal mucosa.

BACKGROUND: The purpose of this study was to investigate the expression and distribution of superoxide anion, NADPH oxidase (NOX)1, and NOX4 in healthy, allergic nasal mucosa and nasal polyps to evaluate the possible influence of oxidative stress on the development of allergic rhinitis and nasal polyps. METHODS: The expression and distribution of superoxide anion, NOX1 and NOX4 were evaluated in healthy and allergic nasal mucosa and nasal polyps, using dihydroethidium fluorescence, semiquantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blot. RESULTS: NOX1 and NOX4 were localized mainly in the epithelial layer, submucosal glands, vascular endothelium, and inflammatory cells in healthy and allergic nasal mucosa and nasal polyps. The cellular source that generated superoxide anion is also localized in the epithelial cells, submucosal glands, vascular endothelium, and inflammatory cells, demonstrating the similar sites of expression of NOX1 and NOX4 in healthy and allergic nasal mucosa and nasal polyps. NOX1 and NOX4 mRNA and proteins and superoxide anions had increased levels of expression in allergic nasal mucosa and nasal polyps compared with healthy nasal mucosa. CONCLUSIONS: These results indicate that NOX1 and NOX4 may play an important role in reactive oxygen species production, contributing to the oxidative stress in allergic rhinitis and nasal polyp tissues.

[Association of xenobiotic-metabolizing gene polymorphisms with childhood atopic diseases in Russian patients from the Republic of Bashkortostan].

Enzymes of biotransformation system involved in the metabolism of exogenous and endogenous compounds are effective mechanism of protection from negative environmental factors. Decreasing activity or insufficient synthesis of biotransformation system enzymes caused by genetic polymorphism form the risk of various complex diseases, including atopic. Using allele-specific hybridization on the biochip the frequencies of xenobiotic-metabolizing gene polymorphisms in Russian children with bronchial asthma, allergic rhinitisand healthy donors from the Republic of Bashkortostan have been determined. The analysis of polymorphisms in CYP1A1, GSTT1, GSTM1, NAT2, MTHFR, CYP2C9 and CYP2C19 genes didn't reveal any association with atopic diseases. The frequencies of CYP2D6*1934G/G genotype and CYP2D6*1934G allele were significantly higher among boys with rhinitis symptoms than in control group.

The urokinase system in patients with intermittent and persistent allergic rhinitis.

Local and systemic changes in hemostasis are associated with allergic diseases. Apart from their well documented role in regulation of plasminogen activation, components of the urokinase system may be involved in modulation of cellular activities during immune inflammatory responses. So far, little has been known about the function of the system in allergic inflammation. In the present study, we assessed circulating levels of the urokinase system components such as urokinase-type plasminogen activator (uPA), soluble form of uPA receptor (CD87), and the inhibitor--plasminogen activator inhibitor type 1. The study comprised of patients suffering from allergic rhinitis, however, without any asthmatic symptoms. Plasma levels of uPA and soluble form of uPA receptor antigens, and plasminogen activator inhibitor type 1 activity were measured in 17 patients with grass pollens-induced intermittent allergic rhinitis and 15 patients with persistent allergic rhinitis due to house dust mite allergy, as well as in 20 sex-matched and age-matched healthy nonatopic participants. We did not observe any statistically significant differences in the levels of the urokinase system components between patients with intermittent allergic rhinitis and persistent allergic rhinitis, and the controls. The circulating levels of uPA, its soluble receptor, and its inhibitor did not differ between allergic rhinitis patients and healthy participants, therefore it seems that the systemic release and activity of the urokinase system molecules may be not significantly changed in the course of nasal allergic inflammation induced by periodic or continuous exposure to a natural allergen.

House dust mite extract induces interleukin-9 expression in human eosinophils.

BACKGROUND: Eosinophils play a pivotal role in allergic inflammation. Recent evidence suggests that they not only function as terminal effector cells but have potential to interact with allergen and initiate immune responses. We investigated cytokine production from eosinophils through direct interaction with a major allergen, house dust mite (HDM) . METHODS: Purified eosinophils from HDM-sensitized or non-sensitized donors were cultured with HDM extract or lipopolysaccharide (LPS) for 18 or 40 h. A panel of cytokine gene expression in eosinophils was examined by means of real-time RT-PCR. Released cytokines in the culture supernatants were assessed with a specific ELISA. In some experiments, HDM was pretreated with protease inhibitors, then added to the culture. Cytokines tested for gene expression were interleukin (IL)-2, 4, 6, 7, 8, 9, 10, 11, 12, 13, 16,17, 18, TGF-beta1 and GM-CSF,. RESULTS: LPS induced small enhancement of GM-CSF gene expression at 18 h. At 40 h, HDM induced about 60-fold enhancement of IL-9 gene expression. IL-9 protein was also detected in the culture supernatants at 60 h. Those reactions were observed regardless of HDM sensitization status of the donors. HDM-induced IL-9 expression was completely inhibited with a serine protease inhibitor, AEBSF, not with a cysteine protease inhibitor, E-64. CONCLUSIONS: Accumulated eosinophils in the airways in asthma may directly react with HDM and produce IL-9 to further promote Th2-type immune responses. Protease-activated receptor 2, a ligand for serine proteases, which contained in HDM, may be involved in the reaction.

Polymorphism at the glutathione S-transferase P1 locus in Korean patients with perennial allergic rhinitis.

BACKGROUND: Oxidative stresses, which induce the reactive oxygen species (ROS), can cause airway inflammation. The glutathione S-transferases (GSTs) protect cells against the effects of ROS. GSTP1 polymorphism may have some effect on allergic rhinitis. Therefore, we have compared the effects of GSTP1 polymorphisms on the perennial allergic rhinitis in Koreans. METHODS: Patients with perennial allergies (149 patients) were selected. The control group included 156 healthy people. Genotypes were evaluated via polymerase chain reaction and restriction fragment length polymorphism, using the Alw26I restriction enzyme. RESULTS: There was no significant difference between groups in the proportions of the Ile/Ile (wild type) and Ile/Val (heterozygote) genotypes. However, the Val/Val (mutant type homozygote) was expressed in only one case (0.7%) in the perennial allergic rhinitis group, as compared with 11 cases (7.1%) in the controls (p < 0.05). CONCLUSION: Our results indicate that the Val/Val genetic polymorphism of GSTP1 may exert some protective effects in allergic inflammation.

Association between angiotensin-converting enzyme gene polymorphism and childhood allergic rhinitis in Taiwan.

BACKGROUND AND PURPOSE: Angiotensin-converting enzyme (ACE) play a role in inactivating bradykinin and tachykinins. Bradykinin and tachykinins are potent mediators of inflammatory reaction. An insertion/deletion polymorphism of the ACE gene has been shown to be associated with serum ACE levels. We hypothesized that ACE polymorphism might play a role in allergic rhinitis development. METHODS: Seventy five children aged 6-13 years with atopic allergic rhinitis and 66 age- and gender-matched healthy children were studied. ACE genotypes were determined by polymerase chain reaction. Serum total immunoglobulin E (IgE) and allergen-specific IgE levels were also measured. RESULTS: The frequencies of the DD and non-DD genotypes, and of the II and non-II genotypes did not differ significantly between healthy children and allergic rhinitis children (chi-squared test, p=1.000 and 0.438, respectively). There was no association of ACE genotype and mean IgE levels in rhinitis children or healthy controls. CONCLUSION: The results of our study indicate that polymorphism of the ACE gene is unrelated to the development of allergic rhinitis, the duration of allergic rhinitis, serum IgE levels, and allergen-specific IgE in Taiwanese children.

Increased expression of inducible nitric oxide synthase in nasal mucosae of guinea pigs with induced allergic rhinitis.

BACKGROUND: Nitric oxide (NO) is produced by the action of NO synthase (NOS) isoforms and is considered an important mediator of inflammatory response including airways. In this study, the changes in the expression levels of NOS isoforms in nasal mucosae were determined in a guinea pig model of allergic rhinitis. METHODS: An allergic rhinitis model was prepared in guinea pigs by repeated challenge with aerosolized dinitrophenylated ovalbumin antigen. Twenty-four hours after the last antigen challenge, the expression levels of NOS isoforms in nasal mucosae were determined by immunoblottings. Changes in the isometrical tension of isolated mucosal tissues of nasal septa induced by histamine were measured also. RESULTS: Although the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in nasal mucosae were not affected by the repeated antigen exposure, the inducible NOS (iNOS) level was markedly and significantly increased in the challenged animals. In isolated nasal mucosal tissues, histamine induced a concentration-dependent relaxation, which was sensitive to an H1-receptor antagonist, mepyramine, and an NOS inhibitor, L-NMMA. No significant change in the histamine responsiveness was observed between the sensitized control and repeatedly antigen-challenged groups. CONCLUSION: The expression of three isoforms of NOS, including eNOS, nNOS, and iNOS, was presented in guinea pig nasal mucosa. A marked increase in iNOS expression in the repeatedly antigen-challenged animals suggests an important role of iNOS in the pathogenesis of allergic rhinitis. However, the pathophysiological role(s) of NO generated by iNOS in nasal allergy is still unclear.

Heme oxygenase (HO)-1 is upregulated in the nasal mucosa with allergic rhinitis.

BACKGROUND: Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. Three isoforms of HO have been discovered. Recently, HO-1 has been found to be upregulated after allergic inflammations of the lower airway. OBJECTIVE: The objective of this study was to address the expression of HO isoenzymes 1 and 2 in the nasal mucosa of patients with allergic rhinitis as well as normal control subjects. METHODS: Nasal mucosa from 30 patients with persistent allergic rhinitis as well as from 10 normal volunteers was used in this study. We used immunofluorescent technique, Western blotting, and real-time quantitative polymerase chain reaction to localize and quantify the expression of these isoenzymes in normal and allergic human nasal tissues. RESULTS: We found that HO-1 is expressed in the epithelial cells of seromucinous glands and macrophages with significant upregulation of its glandular expression in allergic rhinitis but with no difference in its macrophage expression between the study groups in contrast to HO-2 that is expressed in the vascular endothelial lining cells as well as macrophages with no marked difference between the study groups. CONCLUSION: We demonstrated that expression of HO-1, but not HO-2, was upregulated within the nasal tissues in allergic rhinitis inflammation, and understanding the induction of HO-1 expression may provide for better management of allergic rhinitis that involves oxidative stress.

[Expression of heme oxygenase-1 in nasal mucosa of allergic rhinitis guinea pig].

OBJECTIVE: To study the expression of a specific inhibitor of endogenous carbon monoxide (CO) generating enzyme Heme oxygenase-1 (HO-1) in allergic rhinitis guinea pigs. METHOD: Guinea pigs were divided into three groups,one were sensitized by using ovalbumin intraperitoneal and nasal challenge, the second group were treated with dexamethasone as therapy group, the third group were treated with saline for control. The infiltration of eosinophil (EOS) with HE staining and the expression of HO-1 by immunohistochemical staining were observed in nasal mucosa. RESULT: Most of infiltrating cell in mucosa were EOS and the amount of infiltrated EOS related to the level of inflammation,and HO-1 was found mainly located in cell plasma off glandular epithelium of mucosa. The sensitized groups showed that the highest optical densities of HO-1 (P <0. 01) and the most EOS (P < 0.01) were in epithelium, and the therapy group showed lower optical densities of HO-1 (P <0.01) and few of EOS (P <0.01) than sensitized group, but higher than the control group. There was a significant difference between the three groups (P <0.01). CONCLUSION: HO-1 is mainly located in cell plasma of glandular epithelium of nasal mucosa, and the degrees of expression of HO-1 positive correlate with the process of inflammation in allergic rhinitis guinea pigs, which suggests that the endogenous carbon monoxide might play a significant role in the pathogenesis of allergic rhinitis.

[The immunohistochemical observations of NOS in the nasal mucosa of allergic rhinitis animal model of guinea pigs].

OBJECTIVE: To study the immunoreactivity and distribution of both iNOS and eNOS isoforms, and observe the effect of desloratadine on them. METHOD: The guinea pigs were sensitized and challenged followed by harvest of their nasal tissue for immunohistochemical staining. The slides images were semiquantitatively analyzed and compared with the desloratadine treated group and negative control group. RESULT: Both iNOS and eNOS were positively stained in each group. The immunoreactivity of iNOS had no significant difference between groups (P > 0.05), but eNOS had stronger immunoreactivity in the model group and the desloratadine treated group when compared with the negative control group (P < 0.01 and P < 0.05). In addition to the distribution area of iNOS, eNOS was also positive stained in the goblet cells. Desloratadine had no influence on iNOS and eNOS immunoreactivity. CONCLUSION: eNOS might play a more important role than iNOS in regulating the NO level of the nasal tissue of the guinea pigs suffered from allergic rhinitis, and desloratadine had no involvement in regulating the expression of iNOS and eNOS.

Allergen drives class switching to IgE in the nasal mucosa in allergic rhinitis.

IgE-expressing B cells are over 1000 times more frequent in the nasal B cell than the peripheral blood B cell population. We have investigated the provenance of these B cells in the nasal mucosa in allergic rhinitis. It is generally accepted that expression of activation-induced cytidine deaminase and class switch recombination (CSR) occur in lymphoid tissue, implying that IgE-committed B cells must migrate through the circulation to the nasal mucosa. Our detection of mRNA for activation-induced cytidine, multiple germline gene transcripts, and epsilon circle transcripts in the nasal mucosa of allergic, in contrast to nonallergic control subjects, however, indicates that local CSR occurs in allergic rhinitis. The germline gene transcripts and epsilon circle transcripts in grass pollen-allergic subjects are up-regulated during the season and also when biopsies from allergic subjects are incubated with the allergen ex vivo. These results demonstrate that allergen stimulates local CSR to IgE, revealing a potential target for topical therapies in allergic rhinitis.