Barrier dysfunction in the nasal allergy

Epithelial cells form the first physiological barrier against invasion by pathogens and the infiltration of allergens. Tight junctions (TJ), a cell–cell junctional complex located on the apical side of epithelial cells, have a critical role in the maintenance of epithelial barrier function. Impaired TJ structures are observed in patients with asthma, atopic dermatitis and nasal allergy; therefore, the dysfunction of epithelial barriers might be involved in the initiation or progression of allergic diseases. Protease-containing allergens and environmental pollutants enhance paracellular transport in epithelial cells through disruption of epithelial barrier function. This suggests that the disruption of TJ leads to the promotion of allergen delivery into the subepithelia, resulting in the progression of allergic diseases. Thus, protection of the epithelial barrier function might prevent or inhibit the development or exacerbation of allergic diseases. Recently, we reported that diesel exhaust particles (DEP), the main component of particulate patter 2.5, exacerbated allergic rhinitis (AR) in a mouse model through TJ disruption. In addition, we revealed that the oxidative stress-mediated pathway is involved in the effects caused by DEP and that nasal treatment with a reactive oxygen species (ROS) scavenger suppressed DEP-induced TJ disruption and exacerbation of AR. In this review, we focus on the relationship between TJ disruption and allergic disease. Furthermore, we discuss our recent findings regarding TJ disruption and the exacerbation of AR.     

Involvement of vascular endothelial growth factor in nasal obstruction in patients with nasal allergy

It has recently been shown that vascular endothelial growth factor (VEGF) enhances vascular permeability and that mast cells produce VEGF, suggesting the involvement of VEGF in allergic diseases. In the present study we quantitatively analyzed VEGF in the nasal lavage fluid of patients with nasal allergy. We performed nasal antigen challenge with Japanese cedar pollen antigen in 10 healthy adult volunteers and in 10 cedar pollen IgE-positive patients with nasal allergy. In all patients with nasal allergy, VEGF and histamine levels in the nasal lavage fluid reached a peak 30 min after antigen challenge, then returned to prechallenge values 2 h after antigen challenge. In these patients, the histamine level increased three-fold, while the VEGF level increased 10-fold. However, in all healthy adult volunteers, VEGF and histamine levels did not increase. A stronger correlation was noted between the ratio of decreased nasal cavity volume and the ratio of increased VEGF levels (R = 0.823; P < 0.001) than between the ratio of nasal cavity volume and the ratio of increased histamine levels (R = 0.660; P < 0.01). These results suggest that VEGF may contribute to the pathogenesis of nasal obstruction in the early phase of nasal allergy as a new factor involved in increasing vascular permeability.     

Role of nasal allergy in chronic secretory otitis media

Nasal allergy seems to be one of the important causes of chronic secretory otitis media (SOM) in children and adults. Chronic SOM is unequivocally related to disturbed function of the eustachian tube, which facilitates communication of the middle ear with the nasopharynx, nasal cavity, and indirectly with paranasal sinuses. The most serious consequences of chronic SOM are decreased elasticity of the tympanic membrane and hearing impairment. Allergic reactions in the nasal mucosa leading to release of various mediators result in development of three types of nasal response characterized predominantly by nasal obstruction. Eustachian tube functions can be affected directly by the mediators released in the nasal mucosa or indirectly by the nasal obstruction. Nasal challenges with allergens performed by rhinomanometry, combined with tympanometry and eventually audiometry, may be a useful diagnostic supplement for this disorder.     

Effect of dietary vitamin E supplementation on murine nasal allergy.

BACKGROUND: Although many studies have reported the effects of dietary vitamin E on the immune response, none so far has assessed its role in nasal allergy. METHODS: Female BALB/c mice were randomized into two groups and fed a 20% casein diet (control group, 50 mg vitamin E/kg diet) or this diet supplemented with 535 mg vitamin E/kg diet (vitamin E group, 585 mg vitamin E/kg diet) for 4 weeks. During the fifth week, the mice in each group were divided into two subgroups to form a total of four treatment groups: group A (control), group B [control + toluene diisocyanate (TDI) sensitization], group C (vitamin E supplementation), and group D (vitamin E supplementation + TDI sensitization). Groups B and D were treated with two courses of intranasal application of 5% TDI in ethyl acetate, whereas groups A and C were treated with ethyl acetate alone. A week after second sensitization all groups were provoked by applying 2.5% of TDI in the vehicle and nasal allergic responses were observed for 10 minutes. Splenic lymphoproliferation, splenic cell cytokines, and the total serum IgE were measured. RESULTS: Members of group D had lower (P < 0.01) scores of nasal response and sneezed less frequently (P < 0.01) than those of group B. Similarly, splenic lymphoproliferation and production of IL-4 and IL-5 as well as the total serum IgE levels were lower (P < 0.01) in group D than in group B. CONCLUSIONS: The results indicate that higher doses of vitamin E supplementation may suppress nasal allergic responses.     

Honey allergy in adult allergy practice

Honey allergy is a very rare condition which shows a clinical picture ranging from cough to anaphylaxis after ingestion of honey. Here we report 5 cases of honey allergy.     

Serotonin concentration in the spleen

Summary Modifications of previous methods for determining the serotonin concentration of blood and other body tissues are described.The spleen does not appear to release free serotonin into the portal blood. On the contrary, it appears that serotonin is removed from the blood by the spleen. Diseased spleens from human beings and rats have an abnormally low serotonin concentration which is not dependent upon the blood platelet concentration.An unidentified substance, probably chemically related to serotonin, was found spectrophotofluorometrically in 3 human spleens.The study reported in this paper was aided by grant A-3911 from the U.S.P.H.S. and a grant from the California Institute for Cancer Research.     

Serotonin receptors in rat lung

Mammalian lungs have been shown to store and to inactivate serotonin by an active process involving uptake and metabolism. Serotonin has direct action on lung including constrictor effects of pulmonary vascular and tracheobronchial smooth muscle suggesting the presence of serotonin receptors in lung. We have identified several serotonin binding receptors in rat lung. Two separate binding sites are present in a purified mitochondrial fraction. Saturation analysis of (3H)-serotonin binding to outer mitochondrial membranes exhibits temperature-dependent association kinetics and demonstrates a single, high affinity, high capacity binding (dissociation constant = 8.3 +/- 1.2 nM, maximum binding capacity = 0.819 +/- 0.046 pmol/mg protein). The dissociation constant of inner mitochondrial membrane demonstrates a low affinity, low capacity site (dissociation constant = 25.2 +/- 2.2 nM, maximum binding capacity = 0.453 +/- 0.037 pmol/mg protein). The purified microsomal fraction of lung exhibits a moderate affinity, high capacity binding site for (3H)-serotonin (dissociation constant = 14.8 +/- 1.6 nM, maximum binding capacity = 0.760 +/- 0.03 pmol/mg protein). In addition to the lung being the major site for its inactivation, the presence of several specific serotonin receptors may be related to some of the known serotonin actions in lung and may suggest other unknown actions of this amine.     

Serotonin and haemorrheology

One of the crucial determinants of tissue perfusion is the flow behaviour, that is the rheology, of the blood itself. In the microcirculation the most important factor is the ability of the cellular components of blood to deform as they pass through the narrower capillary passages. Until recently, it was thought that the deformability of the red cells was more important than that of the white cells, because of their numerical superiority. Recently, the flow behaviour of white cells is thought to be at least equally important. There is now extensive epidemiological, experimental and clinical evidence linking the microrheological properties of blood to tissue ischaemia. The possible role of serotonin in altering haemorrheology is inferred from studies using specific serotonin antagonists. Ketanserin, given orally has been shown to improve blood filterability in patients with myocardial infarction and intermittent claudication. There was also a specific effect on white cells. It is postulated on the basis of these and other experiments that in situations of tissue ischaemia, when there is a local increase in plasma serotonin levels, the deleterious effect of serotonin on blood cell rheology may have an important role in perpetuating the ischaemia.