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PubMed1995

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis.

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Adolescent↗

PubMed1994

Endothelin-induced vasoconstriction in rabbit nasal mucosa.

Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the effects of endothelin-1 (ET-1), a potent vasoconstrictor peptide, on the blood perfusion of rabbit nasal mucosa by laser Doppler flowmetry. After injection with ET-1, a potent and prolonged nasal vasoconstriction was observed. ET-immunoreactivity has previously been detected in nasal tissues and it is therefore suggested that ET-1 may participate in the regulation of nasal blood flow via paracrine mechanisms.

Animals↗

PubMed1991

Systemic absorption of L- and D-phenylalanine across the rat nasal mucosa.

Nasal absorption of L-phenylalanine (L-Phe) and D-phenylalanine (D-Phe) have been investigated in rats using an in vivo absorption technique. L-Phe was effectively absorbed into systemic circulation with peak plasma level at 45 min after nasal administration. The absolute nasal bioavailability was calculated to be 96.3% when 5 mg/kg dose was given to fasted rats. The absolute bioavailability declined to 66.8% when 12.5 mg/kg of L-Phe was given intranasally while the time to reach peak concentration remained at 45 min. The results substantiated previous in situ data that, despite its high polarity, L-Phe was transported across the rat nasal mucosa into blood stream by the large neutral amino acid (LNAA) carrier. The carrier showed partial saturation at higher doses. On the other hand, when 5 mg/kg of D-Phe was given intranasally, slow and incomplete absorption was observed resulting in a peak time of 60 min and an absolute bioavailability of only 35.2%, suggesting specificity of the carrier for natural L-amino acids.

Administration, Intranasal↗

PubMed1998

Epithelial damage of nasal mucosa in nasal allergy.

Epithelial alterations arising from moderate nasal allergy to house dust were examined and compared to findings in epithelia from nonallergic controls. Biopsy specimens were taken during natural allergen exposure from two different sites: 1) the anterior tip of the inferior turbinate and 2) 2 cm behind it. The tissues were examined by both electron and light microscopy. In the allergic group, epithelial damage was found to be remarkable in the anterior nasal mucosae, where nonciliated cells were prevalent, but minor in the posterior nasal mucosae comprising ciliated and goblet cells. In the anterior nasal mucosae, conspicuous intercellular edema, epithelial shedding, and clusters of eosinophils in the epithelial layer were observed, whereas only a little epithelial shedding and edema in the basal area of the epithelium was noted in the ciliated areas. In controls, pathologic changes were not observed, although a little epithelial shedding was seen in the anterior turbinate. Although there are arguments for and against epithelial shedding in nasal allergy, this study confirms its presence even in patients with moderate allergy.

Adolescent↗

PubMed1999

Distribution of rantes and interleukin-5 in allergic nasal mucosa and nasal polyps.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.

Antibodies, Monoclonal↗

PubMed1989

[Electron microscopic study of glycoconjugate in nasal mucosa of nasal allergy by lectin histochemistry].

Glycoconjugates in glandular and goblet cells of nasal mucosa were compared between normal and nasal allergy by using various horseradish peroxidase (HRP)-conjugated lectins; WGA, PNA, UEA-I and RCA-I. Specific sugar residues of glycoconjugates could be identified under electron microscope. Golgi's complex of the serous secretory cells in nasal allergic mucosa had positive staining in UEA-I. Goblet cells of nasal allergic mucosa were stained strongly in PNA, compared to normal mucosa, however, they were stained weakly in WGA. In conclusion, glycoconjugates in glandular and goblet cells seem to be changed in nasal allergy.

Glycoconjugates↗

PubMed1995

Cytokine gene expression and release from epithelial cells. A comparison study between healthy nasal mucosa and nasal polyps.

BACKGROUND: Epithelial cells release cytokines and they probably contribute to chronic inflammation detected in bronchial asthma, rhinitis and nasal polyposis. OBJECTIVES: To investigate the effect of cultures on cytokine gene expression to compare epithelial cell cytokine release by both healthy nasal nucosa (HNM) and nasal polyps (NP), and the modulation by dexamethasone and to investigate which cytokines may promote eosinophil survival. METHODS: Epithelials cells were cultured to confluence, human epithelial cell conditioned media generated with or without dexamethasone, and supernatants measured by ELISA. Cytokine gene expression was investigated by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fresh epithelial cells only expressed mRNA for intesleukin-8 (IL-8) and granulocyte macrophage-colony stimulating factor (GM-CSF) while cultured cells expressed mRNA for IL-1 beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF alpha) and GM-CSF. Epithelial cells from NP significantly (P < 0.05) released more IL-8 (25431 +/- 3163 pg/mL), and GM-CSF (1229 +/- 391 pg/mL) than those from HNM (18604 +/- 1723 pg/mL for IL-8; and 611 +/- 98 pg/mL for GM-CSF). Dexamethasone 10 microM inhibited the release of all cytokines, this effect being similar (40-50%) in both HNM and NP, except for IL-6 which was higher in HNM. Eosinophil survival induced by epithelial cell secretions from both HNM and NP was strongly blocked by GM-CSF antibody while it was partially blocked by antibodies to TNF alpha and IL-8. CONCLUSIONS: These findings suggest that although epithelial cell culture procedures may upregulate cytokine gene expression, nasal polyps may represent a more active inflammatory tissue by releasing more cytokines than healthy nasal mucosa this release being inhibited by steroids; and that, in addition to GM-CSF, other cytokines such as TNF alpha and IL-8, may also be involved in the promotion of eosinophil survival.

Base Sequence↗

PubMed1998

Localization of nitric oxide synthase in human nasal mucosa with nasal allergy.

Nitric oxide (NO) plays an important role in the regulation of upper respiratory function. In the nasal cavity, the concentration of NO in the air in patients with untreated allergic rhinitis is higher than that in normal individuals. NO is produced by the action of NO synthase (NOS) using L-arginine as a substrate. To investigate the expression of NOS in human nasal mucosa, histochemical staining for NADPH diaphorase and immunohistochemical staining for NOS isoforms were carried out in nasal inferior turbinate mucosa from patients with nasal allergy. Those without nasal allergy served as controls. NADPH diaphorase histochemical study revealed that NOS was expressed in the nasal epithelium, submucosal glands, nerve fibres and the endothelium in specimens of both allergic and control groups. Immunoreactivity to endothelial NOS (eNOS) was localized to epithelial and endothelial cells in both allergic and control groups. In some specimens in both groups, nerve fibres around submucosal glands stained positively for eNOS. Immunoreactivity to eNOS, however, was slightly stronger in the epithelia of the allergic group than in those of the controls. Immunoreactivity to inducible NOS (iNOS) was localized to epithelial cells, endothelial cells, nasal glands and inflammatory cells. The staining of epithelial cells and inflammatory cells was more marked in the allergic group than the controls. These findings may suggest that the greater amounts of NO in the nasal air of patients with allergic rhinitis are mainly induced by iNOS activity.

Case-Control Studies↗

PubMed1978

[Evidence and estimation of immunoglobulins in human nasal mucosa and nasal fluid--a study towards age dependence (author's transl)].

The localization of IgA, IgG and IgM in healthy human nasal mucosa in relation to age--a fluorescence-microscopic study as well as simultaneous quantitative estimation of these immunoglobulins in nasal fluid. These investigations confirm the dominant role of IgA. The IgA concentrations decreases with age. IgG concentration is nearly independent of age. IgM scarlely existing in normal human mucosa and nasal fluid.

Adolescent↗

PubMedDate not supplied

The human respiratory nasal mucosa in nasal syphilis. A histochemical study.

The enzymatic changes in tertiary nasal syphilis were studied in 5 patients. The cholinesterase was increased in the subepithelium, around the glands and blood vessels, denoting parasympathetic hyperactivity. Acid phosphatase was increased in the epithelium, stromal histiocytes, around the glands and ducts, indicating increased phagocytotic activity. Alkaline phosphatase was increased in the capillary endothelium and periglandular stroma, denoting marked vascular changes. Succinic dehydrogenase, alkaline phosphatase, alpha esterase and PAS-alcian blue were diminished in the epithelium and glands, denoting diminished secretory activity, hence a diminished natural defence mechanism of the nasal mucosa. When serological tests are inconclusive, these findings become an important adjuvant to a final diagnosis.

Acid Phosphatase↗

PubMedDate not supplied

The human respiratory nasal mucosa in nasal syphilis. An ultra-microscopic study.

The fine structure of the human tertiary syphilitic nasal mucosa was studied in 5 patients. The epithelium showed variations in thickness, loss of cilia, irregular cell contours, widened intercellular spaces, rare goblet cells. The seromucinous glands were in three forms. The arterioles and capillaries varied in relation to the pathology of the surrounding tissue. The venules were least affected. The stroma was infiltrated by macrophages, plasma cells with some areas having excessive fibrosis and others partially necrotic. These findings were correlated to the histochemical reactions. Scattered Treponema pallidum were seen, demonstrating the blood-borne dissemination and the infective nasal secretions.

Adult↗

PubMed1998

Fibrinolytic components in nasal mucosa and nasal secretion.

We evaluated a possible role for fibrinolytic components in nasal secretion by tissue localization with immunohistochemical techniques and by measuring their antigen concentrations in nasal discharge by means of ELISA and fibrin autography. Nasal mucosa was obtained surgically from the inferior turbinate. Urokinase-type plasminogen activator (u-PA) specific staining was observed in pseudostratified ciliated epithelium and was predominant in mucous cells of the seromucinous gland, while serous cells were almost devoid of stain. The pattern of staining of plasminogen activator inhibitor-2 was similar to that of u-PA. In contrast, plasminogen activator inhibitor-1 (PAI-1) immunoreactive material was localized exclusively in serous cells of seromucinous glands. Positive staining for tissue-type plasminogen activator (t-PA) was observed in endothelial cells and basal cells, which differentiate into either ciliated or goblet cells. Nasal secretions were partially fractionated by immunospecific antibody-immobilized Sepharose. Subsequent fibrin autography patterns indicated the presence of u-PA, PAI-1, and t-PA. After methacholine provocation, the level of t-PA increased transiently but decreased rapidly with subsequent challenges. These differential stainings of fibrinolytic components and the existence of PAs and PAI-1 in the nasal discharge suggest that the fibrinolytic system may play a role in the movement and fluidity of nasal secretion.

Autoradiography↗

PubMed1993

Absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) from rat nasal mucosa.

Nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was examined in the rat. The relative bioavailability of rhG-CSF for subcutaneous administration was approximately 2%, as evaluated from the immunologically active rhG-CSF concentration in rat plasma and the area under the curve (AUC) of the plasma rhG-CSF concentration versus time for 8 hr. Pharmacological availability relative to subcutaneous administration was determined from the increase in total blood leukocyte numbers. The pharmacological availability was 5-10%, determined from the AUC for the increased ratio of total leukocyte numbers versus time for 48 hr; it was slightly dependent on the pH and the osmotic pressure of the dosing solution. Accordingly, the plasma concentration of rhG-CSF did not always reflect its pharmacological effects. Relative bioavailability and pharmacological availability were increased about 23 times and 3 times, respectively, by polyoxyethylene 9-lauryl ether (Laureth-9), but no increase in availability occurred with sodium glycocholate. The increase in total leukocyte numbers was maintained during multiple rhG-CSF dosing, and the addition of Laureth-9 further increased the pharmacological effects of this agent. This study indicates that nasal administration of rhG-CSF is an effective parenteral administration route.

Absorption↗

PubMedDate not supplied

Influence of environmental temperature on human nasal mucosa.

Nasal mucosal blood flow and nasal patency were studied in seven healthy subjects in order to evaluate normal physiological reactions to cold and heat. Blood flow was measured by means of the 133Xe washout method, and nasal patency was determined by measuring maximal nasal expiratory air flow. In comparison with the results at room temperature (23 degrees C), there was a decreased blood flow and a decreased nasal patency after 20 minutes of exposure to cold (6 degrees C). After exposure to heat (40 degrees C), an unaltered blood flow and an increased nasal patency were registered. The results suggest that nasal patency is important for the conditioning of air and support the hypothesis that changes in nasal mucosal blood flow is engaged in body temperature regulation.

Adult↗

PubMed2003

Early events in peripheral regulatory T cell induction via the nasal mucosa.

Nasal application of soluble Ags leads to Ag-specific suppression of systemic immune responses. This tolerance can be transferred to naive mice by CD4(+) regulatory T cells (T(R) cells) from the spleen, but little is known about the induction of mucosal T(R) cells in vivo. To investigate the induction of T(R) cells in the nose-draining cervical lymph node (CLN), CD4(+) T cells from DO11.10 OVA TCR transgenic mice were transferred to BALB/c recipients. Within 48 h after nasal OVA application, CD4(+) DO11.10 T cells in CLN, but not in the peripheral lymph node, had divided. Similarly, nonmucosal (i.m.) OVA application also induced CD4(+) DO11.10 T cells to proliferate in the draining inguinal lymph node (ILN), yet more vigorously and with different kinetics than the CD4(+) DO11.10 T cells in CLN. Functional analysis revealed that only proliferating CD4(+) DO11.10 T cells from CLN, and not ILN, could transfer tolerance to naive recipients. CD4(+) DO11.10 T cells from CLN were phenotypically similar to CD4(+) DO11.10 T cells from ILN, however, in CLN a higher percentage of CD25(+) proliferating CD4(+) DO11.10 T cells were detected compared with ILN. CD25 is not a discriminative marker for mucosal T(R) cells because both CD25(+) and CD25(-) CD4(+) DO11.10 T cells from the CLN could suppress delayed type hypersensitivity responses in adoptive transfer. These findings demonstrate that although striking similarities exist between the differentiation of T(R) and effector T cells, this does not include their function. We are the first to demonstrate that functional T(R) cells, which reside within both CD25(+) and CD25(-) subsets, can be isolated from CLN as early as 3 days after nasal OVA application.

ADP-ribosyl Cyclase↗

PubMed2004

Expression of guanylin and uroguanylin mRNA in human nasal mucosa and nasal polyps.

OBJECTIVES: Guanylin and uroguanylin are small, heat-stable peptides that were originally isolated from the small intestine and from urine, respectively. Functionally, it has been proposed that these peptides can regulate ion and water transport in various fluid-transporting epithelia. In the present study we evaluated the presence of mRNAs for human guanylin and uroguanylin in human inferior turbinate mucosa and nasal polyps. MATERIAL AND METHODS: The expression and localization of mRNAs for both peptides were investigated in inferior turbinate tissues and nasal polyps using reverse transcriptase polymerase chain reaction and in situ hybridization. RESULTS: mRNAs for both peptides were detected in human turbinate mucosa and nasal polyps. In situ hybridization revealed that they were localized in the epithelial layer and submucosal glands of inferior turbinate mucosa and in the epithelial layer of nasal polyps. However, their expression was noted at low levels in the superficial epithelium of nasal polyps, compared with that of inferior turbinate mucosa. CONCLUSIONS: These results indicate that guanylin and uroguanylin in the nasal mucosa may participate in normal physiological processes, but also suggest that altered expression of these genes in nasal polyps may cause impaired electrolyte and water transport across the epithelial cells.

Adult↗

PubMed2005

[The observation of the ciliotoxicity of nasal mucosa with nasal decongestant].

OBJECTIVE: To study the ciliotoxicity of nasalmucosal with nasal decongestant, in order to choose the appropriate nasal decongestant. METHOD: (1) Selected 100 healthy volunteers, by using 0.05% hydrochloride oxymetazoline, 0.025% hydrochloride oxymetazoline, 1.0% ephedrine and 0.5% ephedrine for 7 days with sacchariu technique to test nasal mucociliary transport, and compared with the normal saline. (2) To observe the mucosa of inferior turbinate with Electron Microscopy. RESULT: After using nasal decongestant for 7 days, Mean nasal mucociliary transport rate (MTR) in 0.0500 hydrochloride oxymetazoline groups was (7.64+/-1.56) mm/min and (7.46+/-1.65) mm/min in 0.25% hydrochloride oxymetazoline groups, Mean nasal mucociliary transport rate (MTR) in 1.0% ephedrine groups was (4.73+/-2.03) mm/min and (4.38+/-2.04) mm/min in 0.5% ephedrine groups,The normal saline groups was (7.14+/-1.76) mm/min. MTR was obviously different (F = 16.50, P <0.01). (2)With electron microscopy, it was found that the cilia of epithelial cells were in good order, uniformed in hydrochloride oxymetazoline groups and exfoliated in ephedrine groups. CONCLUSION: Ephedrine has ill effects on nasal mucosa; Hydrochloride oxymetazoline has neither effect on nasal mucosa, nor destroying the physical function of nose, it is an ideal nasal decongestant.

Adolescent↗

PubMed1985

Partial purification and characterization of the tissue plasminogen activator in nasal mucosa and nasal polyp.

Tissue plasminogen activator was partially purified from the inferior turbinate and nasal polyp, and its biochemical properties were investigated. Similar TPA peak positions were seen in the gel filtration chromatography of both tissues, and the molecular weight was approximately 65,000, which was comparable to TPA of pig heart (55,000-60,000). Activity of TPA from inferior turbinate was higher than that from nasal polyp. TPA from both tissues was completely inhibited by trans-aminomethyl cyclohexane carboxylic acid, dithiothreitol, and diisopropylfluorophosphate and had similar inhibition profiles to TPA from pig heart. All these findings indicate that TPA from both tissues is undoubtedly a plasminogen-activating enzyme and serine-type protease and would be biochemically identical.

Chromatography, Gel↗