Leukotriene E4 induces MUC5AC release from human airway epithelial NCI-H292 cells.

BACKGROUND: Hypersecretion of mucin in the airway epithelium is an important feature of allergic airway diseases. Of the 3 cysteinyl leukotrienes (CysLTs; LTC4 LTD4 and LTE4), only LTE4 is sufficiently stable to be detectable in extracellular fluids. However, LTE4 has received little attention because it binds poorly to the CysLT1 and CysLT2 receptors; therefore, little is known about the effects of LTE4 on mucous secretion. Recently, studies have focused on the P2Y12 receptor as a potential receptor for LTE4, because this receptor is required for LTE4-mediated pulmonary inflammation. In our previous study, we confirmed the expression of P2Y12 receptor in human airway epithelial cells. To clarify the roles of LTE4 in airway epithelial cells, we investigated mucus secretion by LTE4 in vitro. METHODS: Confluent NCI-H292 cells were stimulated with LTE4 (0.01-1 µM) for 24 h. The release and production of MUC5AC protein, a gel-forming mucin, were evaluated with an enzyme-linked immunosorbent assay. RESULTS: Western blot analysis revealed that NCI-H292 cells expressed P2Y12 receptor protein. LTE4 significantly induced the release of MUC5AC mucin in a dose-dependent manner. Th2 cytokines such as IL-4 (10 ng/mL) and IL-13 (10 ng/mL) accelerated the LTE4-induced release of MUC5AC protein. MRS2935, a P2Y12 receptor antagonist, partially inhibited the LTE4-induced release of MUC5AC protein in the airway. In contrast, MK571, a CysLT1 receptor antagonist, did not affect the release of MUC5AC protein elicited by LTE4. CONCLUSIONS: These results suggest that LTE4 may play some important roles in allergic mucus secretion partially via activation of P2Y12 receptor.

[Oral Allergy Syndrome Following Soy Milk Ingestion in Patients with Birch Pollen Allergy].

BACKGROUND: Persons allergic to birch pollen often report oral and pharyngeal hypersensitivity to fruit and vegetables, due to immunological cross-reactivity between pollen and foods. This phenomenon is referred to as the oral allergy syndrome (GAS). Such cross-reactive antigen reactions mainly involve Bet v 1, which is the major birch-pollen allergen, and partially involve birch-pollen profilin Bet v 2. Soybean contains Bet v 1-related antigen (Gly m 4), and soy milk often causes the OAS with severe symptoms such as precordial and abdominal burning sensation because soy milk undergoes little denaturation, and this water-soluble liquid is consumed by most people rather quickly. We evaluated the frequency of the oAS after ingestion of soymilk and examined IgE antibodies to various allergens. METHODS: A total of 167 patients [122 women, 45 men; age range, 4-72 years (mean age, 32 years)], who had experienced GAS episodes and had IgE birch--pollen antibodies, were interviewed. Using the CAP system, we examined IgE antibodies to birch pollen and other allergens. Of 167 patients, 161 were examined for IgE antibodies to Bet v 1, Bet v 2, Gly m 4, and soybean. We evaluated the frequency of the GAS after soy milk ingestion based on reports by GAS patients with birch pollen allergy, and evaluated the positive rates of some of the IgE antibodies. RESULTS: Among the 167 patients with birch-pollen allergy and GAS on ingestion of any of the foods, there were 16 cases (10%) with OAS following soy milk ingestion. In addition, the foods that caused OAS most often were apples (123 cases, 74%), peaches (67%), and cherries (55%), followed by pears (37%) and kiwi (37%). A higher CAP class for birch pollen, Bet v 1, Gly m 4, and soybean was associated with a higher prevalence of OAS to soy milk. Of 15 patients who had GAS on ingestion of soy milk and had birch-pollen allergy, 47% (7cases) were CAP class 1 for soybean and only 7% (case) was CAP class c2, whereas 93% (14cases) were CAP class 1 for Gly m 4, and 87% (3cases) were CAP class ≥ 2 for Gly m 4. CONCLUSION: Among the birch-pollen allergic OAS patients, 10% had the OAS on ingestion of soy milk, and among these with birch-pollen allergy and the OAS on ingestion of soy milk, the positive rate for soy milk CAP was low, whereas that for Gly m 4 CAP was high.

[A relationship between birch pollen counts and meteorological factors in Sapporo].

Occurrence of airborne pollen in Sapporo has been studied for 19 years during the period between 1995 and 2013. There are wide year-to-year variations in the quantities of birch pollens. A simple linear regression with the least squares method was used for studying correlations between the annual quantities of birch pollens and the meteorological factors. A significant positive correlation was found between the hours of sunlight in June of the preceding year and the annual birch pollen concentrations with the correlation coefficient, R = 0.667. Also, we found the significant positive correlation between the hours of sunlight in March and the annual birch pollen concentrations with the correlation coefficient, R = 0.684. These results suggest that the atmospheric birch pollen counts can be predicted from meteorological factors.

Expression and localization of purinergic P2Y(12) receptor in human nasal mucosa.

BACKGROUND: Extracellular nucleotides such as ATP and UTP are released from essentially all cells, and they interact with cell surface P2 receptors to produce a broad range of physiological responses. P2Y12 receptor is the major platelet receptor that mediates ADP-induced aggregation, P2Y12 receptor inhibitors such as clopidogrel and prasugrel inhibit platelet aggregation, and thus, they are used in the treatment and prevention of coronary artery disease. Recently, studies have focused on the P2Y12 receptor as a receptor for leukotriene E4 (LTE4), because this receptor is required for LTE4-mediated pulmonary inflammation. To establish the presence of P2Y12 receptor in human nasal mucosa, we investigated the expression and the localization of the P2Y12 receptor in human nasal mucosa. METHODS: Human turbinates were obtained by turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The expression of P2Y12 receptor was evaluated by RT-PCR, western blotting, and immunohistochemical analysis. RESULTS: RT-PCR analysis of total RNA extracted from human nasal turbinate, primary cultured human nasal epithelial cells and nasal vascular endothelial cells demonstrated the expression of P2Y12 receptor mRNA. A band of approximately 55 kDa was detected in human turbinates by western blot analysis using anti-P2Y12 receptor antibody. We could not find any differences between P2Y12 receptor levels in allergic and non-allergic nasal mucosa. An immunohistochemical study revealed that epithelial cells, submucosal glands and vascular endothelial cells showed intense immunoreactivity for the P2Y12 receptor. CONCLUSIONS: The results may have important clinical implications for understanding the role of P2Y12 receptor in upper airway diseases such as allergic rhinitis and non-allergic rhinitis.

Localization and up-regulation of cysteinyl leukotriene-2 receptor in human allergic nasal mucosa.

BACKGROUND: Cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies using CysLTs indicate that 2 classes of receptors exist, namely, CysLT1 and CysLT2 receptors. The former class of receptors is sensitive to the CysLT1 antagonists currently used to treat asthma and allergic rhinitis, and its localization has been previously examined by our group using immunohistochemistry and in situ hybridization techniques. We investigated the expression and localization of the CysLT2 receptor in human nasal mucosa by western blot and immunohistochemical analyses. METHODS: Human turbinates were obtained after turbinectomy from 16 patients with nasal obstruction refractory to medical therapy. To identify the cells expressing the CysLT2 receptor, double immunostaining was performed by using anti-CysLT2 receptor antibody and anti-CD31 (endothelial cell) antibody or anti-smooth muscle actin antibody. RESULTS: A 39 kDa band was detected on the western blots of human turbinates samples by using the anti-CysLT2 receptor antibody. The expression level of the CysLT2 receptor in patients with nasal allergy was higher than that in patients with non-allergic rhinitis. The immunohistochemical study also showed an intense immunoreactivity for CysLT2 receptor in both vascular endothelial cells and vascular smooth muscles. CONCLUSIONS: The results indicated that the CysLT2 receptor plays a primary role in the vascular responses in the upper respiratory tract.

[Questionnaire about the intake of and hypersensitivity to fruits, vegetables and nuts including birch pollen related foods].

BACKGROUND: In Hokkaido and Scandinavia, birch pollen allergic persons are common and they often report oral and pharyngeal hypersensitivity to fruits and vegetables (oral allergy syndrome, OAS), because of immunological cross-reactivity. In Scandinavia, nuts as well as Rosaceae fruits such as apples were the foods most often reported to elicit symptoms. On the other hand, nuts are minor foods causing hypersensitivity in Japan. Even in Japan, regional differences of foods causing hypersensitivity have been reported, which may be related to the regional differences of elementary habit and pollen dispersion. In the present study, we evaluated the intake history of the foods and the frequency of food hypersensitivity in adults from the general population. METHODS: Three hundreds and thirty nine subjects (20-67 years old) took part in the study. With a questionnaire survey, we asked them about their intake history and hypersensitive symptoms for 33 kinds of fruit, vegetables, and nuts. RESULTS: 30% of subjects had eaten Brazil nuts, 80% had eaten pomegranates, and 81% had eaten hazelnuts. And over 95% of subjects had eaten the other 30 foods. Those who had lived in Hokkaido for more than 20 years had a higher frequency of plum consumption than the others. Those who had lived in Hokkaido for more than 20 years had a lower frequency of loquat, fig and pomegranate consumption than the others. Food hypersensitivity was found in 52 subjects (15.3%). The most common symptom was OAS (46 subjects, 13.6%), and foods most frequently causing OAS were peach (21 subjects, 6.2%), cherry (19 subjects, 5.6%) and apple (17 subjects, 5.0%). 26 subjects (7.7%) reported OAS to Rosaceae fruits. The ratio of having OAS to consuming Rosaceae fruits was 11.0% in the group who had lived in Hokkaido for more than 20 years, which was higher than the group who has lived in Hokkaido for less than 20 years. The intake history of hazelnuts and Brazil nuts was very low, with a correspondingly low frequency of food hypersensitivity associated with these nuts. CONCLUSION: The frequency of intake and hypersensitivity of some foods differ among different regions.

Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help.

In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5(-/-) mice exhibited weak antibody responses specific to foreign antigens at the initial and recall phases. This was probably attributable to the low number of follicular and memory B cells and the functional loss of interleukin-21-mediated responses of follicular B cells. Moreover, Alox5(-/-) mice could not fully foster the development of follicular B helper T (Tfh) cells even after immunization with foreign antigens. Further experiments indicated that Alox5 affected mortality in experimentally induced enterocolitis in germ-prone circumstances, indicating that Alox5 would endow immunologic milieu. Our results illustrate the novel role of Alox5 in adaptive humoral immunity by managing primary B cells and Tfh cells in vivo.

Localization and upregulation of the nasal histamine H1 receptor in perennial allergic rhinitis.

In the present study, we have investigated the expression of histamine H1 receptor in human turbinates by RT-PCR, western blotting, and immunohistochemistry. Human turbinates were obtained by turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. RT-PCR analysis of total RNA extracted from human nasal turbinate, primary cultured human nasal epithelial cells, and nasal vascular endothelial cells demonstrated the expression of histamine H1 receptor mRNA. About 56 kDa band was detected in human turbinates by western blot analysis using anti-H1 receptor antibody. The expression level of H1 receptor protein was marked in patients with nasal allergy than in patients with nonallergic rhinitis. The immunohistochemical study revealed that epithelial cells and vascular endothelial cells showed intense immunoreactivity for histamine H1 receptor. In addition, the blood vessels in superficial area expressed higher level of H1 receptor immunoreactivity than that in deeper area in the nasal mucosa. These results may have an important clinical implication for understanding the role of histamine H1 receptor on upper airway diseases such as allergic rhinitis and nonallergic rhinitis.

[Relationship between IgE antibodies to recombinant allergens rBet v 1 and rBet v 2 and food causing oral allergy syndrome in cases of birch-pollen allergy].

BACKGROUND: Persons allergic to birch pollen often report oral and pharyngeal hypersensitivity to fruit and vegetables, such as apples and peaches due to immunological cross-reactivity, or oral allergy syndrome (OAS) sometimes accompanied by systemic reaction. Such cross-reactive antigen reactions involve Bet v 1, the main birch-pollen allergen, and Bet v 2, birch-pollen profilin. We evaluated the food/antigen relationship. METHODS: Subjects interviewed numbered 60-40 women and 20 men aged 12 to 70 (mean age: 35 years)-suffering OAS episodes and having IgE birch-pollen antibodies. Using CAP scoring we examined IgE antibodies to recombinant Bet v 1 (rBet v 1), recombinant Bet v 2 (rBet v 2), and recombinant Pru p 3 (rPru p 3) a peach lipid transfer protein (LTP). A CAP score of 0.35 or more was considered positive. We evaluated the relationship between recombinant allergens and 9 fruit often involving OAS--apple, peach, cherry, kiwi, pear, melon, plum, strawberry, and watermelon-based on subjects' reports. RESULTS: Of the 60, all (100%) were rBet v 1-positive, 9 (15%) rBet v 2-positive, and none (0%) rPru p 3-positive. Rose-family fruit-apples, peaches, cherries, pears, plums, and strawberries-often caused OAS regardless of positive or negative rBet v 2 CAP and were associated with rBet v 1. In contrast, more of those who were rBet v 2 CAP-positive had OAS to non-rose-family fruit-melon and watermelon-than those rBet v 2-negative. In rose-family and non-rose-family classification of the 9 fruit, cluster analysis and kappa statistics showed non-rose-family melon, watermelon, and kiwi to be associated with rBet v 2, as were grass and mugwort pollen allergies. CONCLUSION: Bet v 1 is associated with OAS due to rose-family fruit and Bet v 2 with OAS due to non-rose-family fruit.

Immunohistochemical localization of the bradykinin B1 and B2 receptors in human nasal mucosa.

Bradykinin (BK) has been tobe thought a potent mediator involved in allergic rhinitis because BK was recovered from the nasal lavage fluid of allergic rhinitis patients after allergen provocation and BK receptor antagonists relief nasal allergic symptoms. Two mammalian BK receptor subtypes, B1 and B2, have been defined based on their pharmacological properties. We investigated the localization of these receptors by immunohistochemistry. Human turbinates were obtained after turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. The immunohistochemical study revealed that epithelial cells, submucosal glands, fibroblast, vascular smooth muscle, vascular endothelial cells, and macrophages showed immunoreactivity for both B1 and B2 receptors. The B2 receptor expression was found in peripheral nerve fibers, whereas the B1 expression was not observed in nerves. The results may have an important clinical implication for understanding the differential roles of BK receptor subtypes on upper airway diseases such as allergic rhinitis and nonallergic rhinitis.

[evaluation of relationships between foods and pollen antigens in peach oral allergy patients -serous specific IgE levels of peach recombinant Antigen-].

PURPOSE: Evaluation of the relationships between foods and pollen allergens in oral allergy syndrome (OAS). METHODS: Serous level of specific IgE against recombinant peach allergens (rPru p 1, rPru p 3 and rPru p 4) in 17 peach OAS patients were examined by Pharmacia CAP RASTsystem. RESULTS: In 17 pollinosis patients, the number of patients positive to peach, rPru p 1, rPru p 4 and rPru p 3 RAST were 13 (76%), 14 (82%), 6 (35%) and 0 (0%), respectively. The RAST value of rPru p 1 was significantly correlated with that of natural birch pollen extract (r=0.745, p=0.0003), but not with that of mugwort pollen extract. The RAST value of rPru p 4 was significantly correlated with that of mugwort pollen extract (r=0.602, p=0.0092), but not with that of natural birch pollen extract. CONCLUSION: Concerning to peach OAS, the most important cross-reactive antigen is Pru p 1 in birch pollinosis, and is Pru p 4 in mugwort pollinosis.

[Clustering of food causing oral allergy syndrome in patients with birch pollen allergy].

BACKGROUND: Birch pollen allergic patients often report oral and pharyngeal hypersensitivity to fruits and vegetables such as apples and peaches because of cross-reactivity. This phenomenon, called "oral allergy syndrome" (OAS), is sometimes accompanied by a systemic reaction and is considered to be an IgE-mediated allergy. We evaluated reciprocal relationships between food causing OAS using patient's reports and classified food in patients with birch pollen allergy. METHODS: We interviewed 272 patients who had episodes of OAS and had IgE to birch pollen. Their mean age of the 198 women and 74 men was 34 years (15 to 65). We evaluated the reciprocal relationships between 14 foods frequently causing OAS-apples, peaches, cherries, kiwi, pears, melons, plums, strawberries, persimmons, tomatoes, grapes, watermelons, mangos, and bananas--classifying them by cluster analysis and kappa statistics. RESULTS: The 14 foods were classified into rose-family and non-rose family. Rose-family fruits--apples, peaches, cherries, pears, plums, and strawberries-made a large cluster and were associated reciprocally. Melon and watermelon were associated. Melon and kiwi were not associated with rose-family fruits. Non-rose family foods--kiwi, melons, persimmons, tomatoes, grapes, watermelons, mangos, and bananas-made a large cluster and were partly associated. CONCLUSIONS: Foodstuffs causing OAS were classified into two groups based on patient's reports. Some clusters of foodstuffs were related.

Expression and localization of the thromboxane A2 receptor in human nasal mucosa.

Thromboxane A2 (TXA2) has been thought a potent mediator involved in allergic rhinitis, because TXA2 was recovered from the nasal lavage fluid of allergic rhinitis patients after allergen provocation and TXA2 receptor antagonists relief nasal allergic symptoms. In order to clarify the expression of TXA2 receptor in human nasal mucosa, we investigated TXA2 receptor mRNA expression and its protein localization by polymerase chain reaction (PCR) and immunohistochemistry, respectively. Human turbinates were obtained after turbinectomy from 10 patients with nasal obstruction refractory to medical therapy. RT-PCR analysis of total RNA from nasal mucosa demonstrated the expression of TXA2 receptor alpha mRNA. The immunohistochemical studies revealed that anti-TXA2 receptor alpha antibody labeled vascular smooth muscle cells, vascular endothelial cells, epithelial cells and submucosal glands in the nasal mucosa. The results may have an important clinical implication for understanding the role of TXA2 receptor on upper airway diseases such as allergic rhinitis and non-allergic rhinitis.

Capsaicin induces the production of IL-6 in human upper respiratory epithelial cells.

Capsaicin, a type of alkaloid and the pungent component of chili peppers, is used as a therapeutic drug against allergic rhinitis and also as an index of bronchial hypersensitivity. Capsaicin receptor (TRPV1) expression has been identified in non-neuronal cells as well as neuronal cells. In our previous study, both TRPV1 protein and its gene expression on nasal epithelial cells were confirmed by immunohistochemistry and RT-PCR, respectively. In order to clarify whether or not TRPV1 acts as a functional receptor, we examined the effects of capsaicin on the production of IL-6 from primary cultured human airway epithelial cells at both protein and mRNA levels. Human nasal epithelial cells (HNECs) and normal human bronchial/tracheal epithelial cells (NHBE cells) were stimulated with increasing concentrations of capsaicin and/or pretreatment with capsazepine (TRPV1 antagonist) at 37 degrees C. The supernatant and total RNA were collected at 0, 4, 12, 24 and 48 h after treatment. IL-6 concentration and the IL-6 mRNA level were evaluated by ELISA and real-time PCR, respectively. Capsaicin (10 nM-10 muM) induced production of IL-6 from HNECs and NHBE cells and this effect was inhibited by pretreatment with capsazepine. Our findings suggest that topical application of capsaicin to the airway induces IL-6 production from respiratory epithelial cells via activation of TRPV1.

Expression and localization of GPR99 in human nasal mucosa.

OBJECTIVE: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic rhinitis. Pharmacological studies of CysLTs indicate that two classes of receptors, CysLT1R and CysLT2R exist. CysLT1R is a high affinity LTD4 receptor with lower affinity for LTC4, and a CysLT1R antagonist is currently used to treat asthma and allergic rhinitis. CysLT2R binds to LTC4 and LTD4 with equal affinity. GPR99 (also called GPR80), previously described as an oxoglutarate receptor (OXGR1), has recently emerged as a potential novel receptor with LTE4. The purpose of this study was to determine the expression and localization of GPR99 protein in the human nasal mucosa. METHODS: Human turbinates were obtained after turbinectomy from 12 patients with nasal obstruction refractory to medical therapy. GPR99 protein expression was evaluated by western blotting, and the specific cells expressing GPR99 protein identified by immunostaining using a commercial anti-GPR99 (OXGR1) monoclonal antibody. RESULTS: A 38-kDa band was detected in the western blots of human nasal samples by using the anti-GPR99 monoclonal antibody. We did not find any differences in GPR99 protein levels between allergic and non-allergic nasal mucosa. The immunohistochemical studies revealed that the anti-GPR99 monoclonal antibody mainly labeled vascular smooth muscle cells in the nasal mucosa. CONCLUSION: These immunohistochemical results suggest that GPR99 may play some roles in the vascular response. Further functional studies will be necessary to clarify the biological significance of the GPR99 receptor in nasal vasculature.

Leukotriene D4 induces chemotaxis in human eosinophilc cell line, EoL-1 cells via CysLT1 receptor activation.

Numerous reports have shown that cysteinyl leukotrienes (CysLTs) contribute to tissue accumulation of eosinophils in allergic airway inflammation. To date, only a few studies have reported that CysLTs promote chemotactic activity of human eosinophils in vitro. The purpose of this study was to investigate whether CysLTs promote chemotaxis in the human eosinophilic cell line, EoL-1. EoL-1 cells were induced to differentiate into mature eosinophil-like cells via incubation with butyric acid and cytokines (IL-3, IL-5 and GM-CSF). The chemotactic activity of the differentiated EoL-1 cells was assessed using the commercial cell migration assay kit. LTD4 elicited dose-related chemotactic activity in the differntiated EoL-1 cells in the range of 1-100 nM. A typical bell-shaped dose-response curve was observed with optimal activity at 10 nM. The chemotactic activity elicited by LTD4 (10 nM) was significantly inhibited by montelukast (control, 345 ± 19.2 × 103 RFU; LTD4 10 nM alone, 511 ± 39.2 × 103 RFU; LTD4 10 nM plus montelukast 100 nM, 387 ± 28.2 × 103 RFU). LTD4 induces migration in eosinophilic cells via activation of CysLT1 receptor. The present in vitro model may be useful for elucidation of the mechanism underlying CysLT-induced tissue eosinophilia.

Clinical benefit of component-resolved diagnosis in Japanese birch-allergic patients with a convincing history of apple or peach allergy.

OBJECTIVE: In northern Japan, birch pollen is the major allergen in pollinosis, while oral allergy syndrome (OAS) is caused primarily by apple and peach, and is almost exclusively related to birch pollinosis. To clarify the clinical benefit of allergen-based component-resolved diagnosis (CRD) in Japanese birch-allergic patients with OAS, we present an analysis of IgE profiles in response to crude extracts and recombinant component-resolved allergen to birch pollen and Rosaceae fruits allergens. METHODS: The sera of 30 patients with birch pollen-related OAS to apple or peach were analyzed for specific IgE reactivity to pathogenesis-related class 10 (PR-10) family (birch: rBet v 1, apple: rMal d 1, and peach: rPru p 1), profilin (birch: rBet v 2 and peach: rPru p 4), and lipid transfer protein (LTP) (apple: rMal d 3 and peach: rPru p 3) allergens, as well as to conventional crude, unfractionated extracts (birch: T3, apple: f49, and peach: f95) using the ImmunoCAP System™. Allergen-specific IgE values <0.35kUA/L were considered negative. RESULTS: Of the 30 sera CAP-positive for natural birch pollen extract, 28 (93.3%) exhibited specific IgE against Bet v1, and two (6.7%) contained specific IgE against Bet v2. Of the 26 sera of OAS to apple patients, only 17 were positive for specific IgE against f49 extract (65.4%); however, 24 were positive for specific IgE against rMal d 1 (92.3%). Similarly, only 17 of the 23 sera of OAS to peach patients contained specific IgE against the f95 extract (73.9%); however, 22 were positive for specific IgE against rPru p 1 (95.7%). CONCLUSION: Our data suggest that CRD constitutes a reliable tool for the diagnosis of birch pollen-related OAS.

Distribution of specific binding sites for cysteinyl leukotriene 1 receptor antagonist in human nasal mucosa.

CONCLUSION: The high density of [3H]-pranlukast binding sites on the local leukocytes in human nasal mucosa suggests that CysLT1 receptor antagonists may directly modulate cellular function of the local leukocytes through binding to CysLT1 receptor on allergic nasal mucosa. OBJECTIVES: The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that two classes of receptors named CysLT1 and CysLT2 receptor exist. The former is sensitive to the CysLT1 receptor antagonist currently used to treat asthma and allergic rhinitis. To confirm the binding sites of CysLT1 receptor antagonist in human nasal mucosa, the autoradiographic distribution of CysLT1 receptor was studied in human nasal inferior turbinates. MATERIALS AND METHODS: Cryostat sections were incubated with [3H]-pranlukast for autoradiography. Nonspecific binding was determined by adding unlabelled pranlukast. RESULTS: Autoradiograms indicated [3H]-pranlukast densely labeled on the interstitial cells. Blood vessels were sparsely labeled. There was no specific labeling in the submucosal glands or epithelium. These results support our previous report from in situ hybridization and immunohistochemistry of CysLT1 receptor.