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HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed epithelial tight junctions in human nasal mucosa of allergic rhinitis.

The epithelial barrier of the upper respiratory tract plays a crucial role in host defense. In this study, to elucidate whether there is antigen monitoring by dendritic cells (DCs) beyond the epithelial tight-junction barrier in allergic rhinitis, we investigated the expression and function of tight junctions and characterized DCs in the epithelium of nasal mucosa from patients with allergic rhinitis. In reverse transcription-polymerase chain reaction, mRNAs of tight-junction proteins occludin, JAM-1, ZO-1, and claudin-1, -4, -7, -8, -12, -13, and -14 were detected in the nasal mucosa. Occludin, JAM-1, and ZO-1 were colocalized in the uppermost layer in the pseudostratified epithelium of the nasal mucosa, whereas claudin-1, -4, and -7 were found throughout the epithelium. In freeze-fracture replicas of the nasal mucosa, continuous tight-junction strands formed well-developed networks. Epithelial barrier function measured by a dye tracer was well maintained in occludin-positive tight junctions in the epithelium of the nasal mucosa. HLA-DR- and CD11c-positive DCs expressed claudin-1 and penetrated beyond occludin in the epithelium of the nasal mucosa with, but not without, allergic rhinitis. These results indicate that DCs may easily access antigens beyond epithelial tight junctions in the human nasal mucosa of allergic rhinitis.

Adult↗

Expression of platelet-derived endothelial cell growth factor and vascularity in the nasal mucosa from allergic rhinitis.

BACKGROUND: Angiogenesis plays critical roles in various pathological mechanisms. It has been hypothesized that the vascularity in allergic nasal mucosa is different from that in normal mucosa, and that changes in the vascular network contributes the pathogenesis of allergic rhinitis. OBJECTIVE: To determine whether hypervascularity and overexpression of the platelet-derived endothelial cell growth factor (PD-ECGF), an angiogenic factor, are found in allergic nasal mucosa and whether these two factors are associated with the allergic reaction. METHODS: We investigated the expression of PD-ECGF and counted microvessels in 51 nasal mucosae (30 samples from patients with allergic rhinitis and 21 samples as control from normal subjects) using an immunohistochemical technique. RESULTS: PD-ECGF expression in allergic nasal mucosae was significantly higher than that in control mucosae at the interstitium of the lamina propria (P = 0.0024) and nasal gland (P = 0.024). PD-ECGF positive areas were coincident with areas of high vascularity in the sections. The microvessel count in the lamina propria of allergic mucosae was higher than that of control mucosae (P = 0.050). Regarding the correlation with various clinical factors, the total nasal symptom score was significantly associated with both the PD-ECGF expression in the interstitium of the lamina propria (P < 0.05) and in the nasal gland (P < 0.005), as well as with the number of vessels (P < 0.05). CONCLUSION: PD-ECGF and hypervascularity in the nasal mucosa may be involved in the pathogenesis of allergic rhinitis.

Blood Platelets↗

Ruthenium red antagonism of capsaicin-induced vascular changes in the rat nasal mucosa.

Mechanisms of capsaicin-induced vascular changes were examined in the nasal mucosa of anesthetized adult rats. Intra-arterial infusions of capsaicin at doses of 20-100 pmol/min into the external carotid artery resulted in a dose-dependent increase in nasal blood flow as assessed by laser-Doppler flowmetry. Intra-arterial infusion of ruthenium red (RR, 2.5-10 mumol) prior to the administration of capsaicin significantly inhibited the capsaicin-evoked response. The technique of vascular labelling was used to examine nasal mucosal vascular permeability. Intravenous administration of colloidal silver solution prior to capsaicin infusion resulted in accumulation of colloid in the walls of small blood vessels, indicative of enhanced vascular permeability. Vascular labelling was largely abolished after RR pretreatment. These findings suggest that neuropeptides released from trigeminal sensory nerve endings play a significant role in the local vascular and inflammatory reactions of the nasal mucosa. The experimental approach utilized in this study provides a promising model for defining the roles of capsaicin-sensitive afferent nerves in the mechanisms of allergic and/or inflammatory diseases affecting the nasal mucosa.

Animals↗

Vascular control of the pig nasal mucosa: distribution and effect of somatostatin in relation to noradrenaline and neuropeptide Y.

By means of immunohistochemistry and radioimmunoassay (RIA), we have investigated the possible occurrence of somatostatin (SOM)-like immunoreactivity (-LI) in the autonomic innervation of the pig nasal mucosa. SOM-immunoreactive (-IR) fibres were present around nasal arteries, arterioles and venous sinusoids. Double-labelling experiments revealed that SOM-LI was co-localized with the noradrenaline (NA) markers tyrosine hydroxylase and dopamine-beta-hydroxylase as well as with neuropeptide Y (NPY) in a subpopulation of neurons in the superior cervical sympathetic ganglion and in perivascular nerve terminals. Furthermore, SOM-LI was also present in perivascular fibres containing vasoactive intestinal polypeptide (VIP) and NPY of presumably parasympathetic origin. The parasympathetic fibres that were associated with glands contained peptide histidine isoleucine (PHI), VIP and NPY but not SOM, suggesting that in the nasal mucosa SOM-IR is restricted to perivascular nerves. As revealed by RIA, the content of SOM-LI in biopsies of both nasal mucosa and superior cervical sympathetic ganglion was about 12 pmol/g and the reverse phase HPLC characterisation of SOM-LI shown two separate peaks for SOM-28 and SOM-14. In thiopentone anaesthetized pigs (n = 10), local intra-arterial (i.a.) infusion of SOM (1-14) induced dose-dependent, long lasting and parallel reduction of the nasal arterial blood flow, the volume of the nasal mucosa (reflecting capacitance vessel function) and decrease of the laser Doppler flowmeter signal (reflecting superficial nasal mucosal blood flow). These functional responses were not modified after pretreatment with the alpha-adrenoceptor antagonist phenoxybenzamine (1 mg kg-1 i.a.) whereas the effects of NA were almost abolished. SOM (6.10(-6) mol, i.a.) did not influence the nasal vascular responses to single impulse stimulation of the nasal sympathetic nerve supply providing no evidence for prejunctional activity in spite of clear-cut vascular effects. It is concluded that SOM-LI is co-localized with NA and NPY in sympathetic nerves and with VIP/NPY in parasympathetic perivascular nerves of the pig nasal mucosa. Since SOM evokes vasoconstriction via non-adrenergic mechanisms, this peptide should also be considered when discussing mediator candidates for the neural regulation of the nasal vascular bed.

Animals↗

[Changes of microcirculation in nasal mucosa during -15 degrees head-down tilt].

Changes of microcirculation in nasal mucosa in 19 young men during 2.5 h head-down -15 degrees tilt (DHT) were observed with Laser Doppler Flowmetry. The results showed that the change of microcirculation in nasal mucosa was significant, blood volume, concentration and the velocity of blood flow increased, and distinct periodical wave of microvessels appeared during HDT. The results suggest that the change of microcirculation in nasal mucosa caused by fluid shift from the lower to the upper body is one of the important factors causing stuffy nose and breathe with a little difficulty.

Aerospace Medicine↗

Lectin histochemistry of normal and herpesvirus-infected bovine nasal mucosa.

Proliferation of Pasteurella haemolytica serotype 1 in the nasal cavity following stress or viral infection is an important event in the pathogenesis of bovine pneumonic pasteurellosis. Enhanced adhesion of P. haemolytica to nasal mucosa could be one factor that predisposes animals to this proliferation. Nasal mucosa from normal and bovine herpesvirus-1 (BHV1)-infected cattle were examined histochemically for their glycoconjugate composition. Twenty lectins were screened, six of which were chosen for subsequent study. Three of these were specific for N-acetylgalactosamine (NAGal) (Dolichos biflorus, Glycine max, and Vicia villosa), and one each was specific for N-acetylgalactosamine/galactose (Griffonia simplicifolia-I), mannose/glucose (Canavalia ensiformis), and N-acetylglucosamine (Triticum vulgaris). For the surface mucosa and submucosal glands, there was greater reactivity in samples from BHV1-infected than from normal cattle for all six lectins. Reactivity was most prominent for the NAGal-specific lectins. Neuraminidase treatment of samples from normal and BHV1-infected cattle tended to result in greater lectin reactivity. Lectin reactivity was generally more intense in focally inflamed areas, but diffuse reactivity was not substantially affected by inflammation. BHV1-induced alteration of nasal mucosal glycoconjugates could enhance adhesion and colonization of P. haemolytica to nasal surfaces and may be one factor responsible for the increased number of P. haemolytica serotype 1 in the nasal cavity following viral infection.

Animals↗

Tissue density and state of activation of eosinophils in the nasal mucosa of allergic and nonallergic rhinopathic patients.

The tissue density of eosinophils and the degree of activation of eosinophils in the nasal mucosa of allergic and nonallergic rhinopathic patients were studied by a combination of the immunogold method, which uses EG2 antibody which binds to the secreted form of eosinophils, and the Luna method. The tissue density of eosinophils and the degree of EG2-positivity were higher in the allergic nasal mucosa than in the nonallergic nasal mucosa. The eosinophils in the tissue were mainly EG2-positive in contrast with those in the vessels. Epithelial shedding was rarely observed and was not related to the tissue density of eosinophils or EG2-positivity. Our results suggest that the eosinophils in the allergic nasal mucosa are activated in the tissue, not in the vessel.

Adolescent↗

Interferon-alpha affects the tumour necrosis factor-alpha content of mast cells in human nasal mucosa. A pilot study in allergic patients.

Human nasal mucosal mast cells contain and secrete tumour necrosis factor (TNF)-alpha, which in turn can stimulate histamine secretion by these cells. Interferon (IFN)-alpha can inhibit TNF-alpha secretion by mast cells in vitro. We have addressed the interrelationships between IFN-alpha and the content in TNF-alpha and number of mast cells in vivo, in the human nasal mucosa. Biopsies were taken from two healthy control patients, two allergic patients and two more allergic patients treated topically with IFN-alpha for two weeks; biopsies from the last two patients were taken both before and after stimulation with the specific allergen. Mast cells were counted upon tagging with rhodaminated avidin and by indirect immunofluorescence for TNF-alpha. Data were subjected to analysis of variance. Mast cell numbers were significantly lower in all allergic patients than in controls (P<0.001). Upon IFN-alpha treatment, TNF-alpha positive mast cells were less than in allergic, untreated patients and the opposite was true for TNF-alpha negative mast cells (p<0.05). Allergen challenge caused selective, significant decrease only in the number of TNF-alpha negative mast cells (p<0.05). The results suggest that upon topical IFN-alpha treatment: (1) mast cells stores of TNF-alpha in the nasal mucosa of allergic patients are decreased; and (2) only TNF-alpha negative cells degranulate in response to allergen challenge. Therefore, one may expect that such a treatment reduces the TNF-alpha burden to the mucosa in these patients.

Adult↗

Passive smoking causes an 'allergic' cell infiltrate in the nasal mucosa of non-atopic children.

Environmental tobacco smoke (ETS) is one of the most common indoor pollutants to which many children are exposed. This study was set up to determine possible effects on cellular infiltrates in the nasal mucosa of children exposed to ETS. The research population consisted of a group of ten children exposed to more then 15 cigarettes/day and a control group of ten children without exposure. The groups were matched for age and gender. None of the children had an atopic constitution. Immunohistochemical staining techniques were used to determine the number of Langerhans cells, T cells, B cells, granulocytes, macrophages, mast cells and eosinophils in the nasal mucosa. IgE+ cells and eosinophils were seen in significantly higher cell numbers in the nasal mucosa of children exposed to ETS (Mann-Whitney U-test). IgE+ mast cells were not found to be more numerous in the ETS-exposed group. We can conclude that exposure to ETS causes changes in cellular infiltrates which partly resemble those seen in the nasal mucosa of allergic children. However, no sign of allergic sensitisation can be found in the nasal mucosa. Children with a genetic predisposition to allergic disease will probably suffer most from the 'unstable' nasal mucosa due to ETS.

Air Pollution, Indoor↗

Lymphocyte and mast cell counts are increased in the nasal mucosa in symptomatic natural colds.

Knowledge of the virus-induced immune response is important in understanding the pathophysiology of respiratory virus infections. Data on the cellular immune response is still limited and based mainly on experimental studies. Natural colds may differ in their pathophysiology from experimentally induced ones. To evaluate the inflammatory cell responses in the upper respiratory tract during natural colds we counted the number of lymphocytes, mast cells and macrophages in the nasal mucosa. Nasal biopsies were taken from 22 adult volunteers during the acute (2-4 days of symptoms) and convalescent phases (day 21) of the cold, and the numbers of cells were counted with immunohistochemical methods. Viral aetiology was identified in 14 (64%) subjects by using viral isolation, antigen detection and rhino-polymerase chain reaction assays. The number of T lymphocytes was increased in the nasal epithelium and that of T and B lymphocytes and mast cells in the subepithelial layer in the acute phase compared to the convalescent phase. Intraepithelial T lymphocyte counts were significantly higher in the subjects who had a proven viral infection or a finding of pathogenic bacteria in the nasopharynx compared to the subjects without such findings (P = 0.005 and P = 0.04, respectively). Contrary to the earlier experimental studies, we found that viruses cause accumulation of T and B lymphocytes and mast cells during the first days of a symptomatic naturally acquired respiratory infection.

Acute Disease↗

Regenerating human nasal mucosa cells express peptide growth factors.

The goal of this study was to investigate if the distribution of peptide growth factors in the human nasal mucosa could be correlated to its maintenance and to repair processes. Biopsy specimens from clinically healthy humans, aged 6 months to 70 years, were investigated immunohistochemically. In the intact human nasal mucosa, only scattered basal epithelial cells and rare, randomly distributed cells in the lamina propria expressed peptide growth factor immunoreactivity. In contrast, in areas with deficient epithelial lining and infiltration of inflammatory cells, intense insulinlike growth factor I immunoreactivity was demonstrable in reactive epithelial cells, while adjacent, more differentiated cells were nonreactive. Vascular wall cells, fibroblasts, macrophages, and exocrine gland cells in the reactive nasal mucosa showed variable insulinlike growth factor I immunoreactivity and, at lower frequencies and intensities, immunoreactivity to insulinlike growth factor II, basic fibroblast growth factor, platelet-derived growth factor, and transforming growth factor beta, as did cells in the normally nonreactive exocrine glands. Macrophages and vascular smooth-muscle cells could in addition express platelet-derived growth factor immunoreactivity. Increased cell proliferation was recognized in reactive areas of the nasal mucosa specimens, ie, in those concomitantly showing distinct peptide growth factor immunoreactivity. We concluded that a complex pattern of peptide growth factor immunoreactivity is transiently expressed by reactive and regenerating nasal mucosal cells, contrasting with the nonreactive normal, differentiated cells. The close correlation between the appearance of peptide growth factors and the local repair and maintenance processes supports our working hypothesis that peptide growth factors are of functional importance for the nasal mucosa.

Adolescent↗

Histopathologic examination and enumeration of polymorphonuclear leukocytes in the nasal mucosa during experimental rhinovirus colds.

The histology of the nasal mucosa was examined by serial scrape and punch biopsies in 20 rhinovirus infected volunteers and 10 sham inoculated controls. No morphologic changes could be detected in the epithelial or subepithelial portions in the mucosa of specimens from infected volunteers. There was a significant increase in the number of polymorphonuclear leukocytes (PMNs) in the nasal epithelium of the infected subjects early in the course of the cold compared to their pre-infection baseline. However, trauma to the nasal mucosa from repeated sampling led to an outpouring of PMNs into nasal mucus, making evaluation of the results difficult. The number of mast cells seen in the mucosal specimens of the infected subjects did not differ from that seen in controls.

Adult↗

The isolation of prostaglandin E from pig nasal mucosa.

Prostaglandins of the E series (PGE) have been shown to be potent nasal vasoconstrictors but have not previously been isolated from the nasal mucosa. Here we report the isolation of a biologically active substance with properties similar to PGE from pig nasal mucosa. The substance was identified as PGE on the following criteria: 1 our isolation procedure demonstrated the presence of a biologically active polar acidic lipid; 2 caused contractions of the isolated rat stomach fundic strip similar to PGE2; 3 caused a prolonged nasal vasoconstriction similar to PGE2; 4 travelled on thin layer chromatogram with PGE. The PGE found in the nasal mucosa may have a role in the regulation of mucosal blood flow in normal and pathological conditions.

Animals↗

[Ultrastructural changes in human nasal mucosa in rhinitis medicamentosa].

BACKGROUND: Long-term abuse of decongestive nasal drops causes rhinitis medicamentosa due to cytotoxic and ciliary-toxic effects. Nasal obstruction is caused by rebound swelling when the decongestive effect has disappeared. The patient starts using nasal drops more frequently as a result of tachyphylaxis. PATIENTS AND METHODS: Tissue samples from human inferior turbinates from 22 patients who had overused decongestive nose drops were taken during nasal surgery and preserved in phosphate-buffered paraformaldehyde or glutaraldehyde. Ultrathin sections were cut. The samples were dehydrated and embedded in Araldit. The findings were photo-documented using a light- and transmission electron microscope. Biopsies from ten patients without chronic inflammation of the nasal mucosa were used as controls. RESULTS: The electron microscopic investigations revealed epithelium showing severe damage corresponding to regions with hyperplastic and metaplastic changes. Loss of ciliated cells was observed. Under a thick basal membrane, ultrastructural changes to the endothelial lining, such as openings and rupture of the basal lamina, were detected. Prominent endothelial cells were conspicuous. CONCLUSIONS: Rhinitis medicamentosa is a drug-induced injury to human nasal mucosa associated with the prolonged abuse of topical nasal decongestants. Loss and destruction of ciliated epithelial cells are the morphological correlation to the disturbance of mucociliary clearance. Endothelial cells of capillaries, in particular, revealed ultrastructural changes indicative of increased permeability with consecutive interstitial edema.

Administration, Intranasal↗

Effects of beclomethasone dipropionate aerosol on nasal mucosa.

Rhinoscopic examination and histological studies of the nasal mucosa in patients with perennial allergic rhinitis and nasal polyposis treated with beclomethasone dipropionate aerosol provided no evidence that this form of treatment, given for one year, produced any harmful effects, such as atrophic rhinitis.

Aerosols↗

Vasoactive substances in the nasal mucosa.

Besides histamine another smooth muscle stimulating substance has been found in the nasal mucosa of dog and sheep. It is an acid which is readily oxidized by neutral aqueous potassium permanganate and osmium tetroxide, and is thermostable at pH 10.8 but not at pH 2.8. The purification of this acid has been followed by using the atropinized tortoise intestine as a test object, which is insensitive to acetylcholine, 5-hydroxytryptamine and small amounts of histamine. Both the tortoise intestine and rat colon are contracted by this acidic substance. The amount of histamine found in sheep nasal mucosa ranged from 12 to 23 mug./g. tissue and in dog nasal mucosa from 6 to 13 mug./g. tissue.

Acetylcholine↗

Effects of capsaicin on human nasal mucosa.

In order to determine the effects of capsaicin on the sympathetic innervation of human nasal mucosa, the effects of capsaicin on the contractile response of isolated human nasal mucosal blood vessels to field stimulation and methoxamine were investigated. Results showed that capsaicin enhanced field stimulation but there were no effects on mucosal contraction induced by methoxamine. Likewise, the drug had no effects on mucosal basal tension but potentiated mucosal contractions by norepinephrine. The study indicated that capsaicin may increase sympathetic function with the potentiating effects of norepinephrine. Because no effects of capsaicin on the resting tension of the nasal mucosa in vitro were noted, it is therefore deduced that local reactions in nasal mucosa by capsaicin in vivo should be via central or local reflexes.

Capsaicin↗

Distribution of immunocompetent cells in normal nasal mucosa: comparisons among germ-free, specific pathogen-free, and conventional mice.

To better understand the role of immunocompetent cells in the defense mechanism of the upper respiratory tract against microbial invasions, the distribution patterns of those cells were investigated in nasal mucosa of mice maintained in three different conditions: germ-free (GF), specific pathogen-free (SPF), and conventional (CV) conditions. Immunostaining by the indirect peroxidase method and toluidine blue staining were employed for the detection of immunocompetent cells and mast cells. For immunostaining, anti-IgG, -IgA, and -IgM polyclonal antibodies and anti-Lyt-1, -Lyt-2, and -Mac-1 monoclonal antibodies were used as primary antibodies. In nasal mucosa of CV mice, Mac-1+ cells, mast cells, and all cell types of lymphocyte subsets were present. In nasal mucosa of SPF mice, all cell types were also positive, but fewer in number than those of CV mice. In nasal mucosa of GF mice, IgG+, IgA+, and Lyt-2+ cells were rare, although IgM+ and Lyt-1+ cells were present in small numbers. An electron microscopic study revealed that follicle-like lymphocyte aggregates with high endothelial venules were present in nasal mucosa close to the mucosal epithelia. These findings suggest that lymphocytes are mobilized to nasal mucosa, responding to continuous antigenic stimuli, and play an important role in the local defense mechanism of the upper respiratory tract.

Animals↗