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Expression of ecalectin, a novel eosinophil chemoattractant, in nasal polyps.

CONCLUSION: Ecalectin, which is produced in the mucosa of nasal polyps, seems to play an important role in the accumulation and activation of eosinophils in nasal polyps, regardless of the presence or absence of atopic predisposition. OBJECTIVE: Ecalectin is a recently discovered eosinophil chemoattractant which elongs to the galectin family. We investigated the expression of ecalectin in nasal polyp tissues associated with various nasal and paranasal diseases in order to clarify the pathogenesis of eosinophilia in nasal polyposis. MATERIAL AND METHODS: Nasal polyps were taken from 56 patients diagnosed as having chronic sinusitis with nasal polyposis. The surgically resected polyps and nasal turbinates were immunohistochemically stained using antibodies against EG2, human mast cell tryptase, CD3 and ecalectin. RESULTS: The number of EG2- and ecalectin-positive cells was significantly higher in nasal polyps than control turbinates. Ecalectin-positive cells were observed in the subepithelial layer, where many EG2-positive cells were present. The number of ecalectin-positive cells correlated significantly with the number of EG2-positive cells in nasal polyps. Many ecalectin mRNA-positive cells were also observed in nasal polyps with an accumulation of EG2-positive cells.

Adolescent↗

[Expression of tenascin in human nasal polyp tissue and primary studies of its clinical significance].

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of tenascin in human nasal polyps. METHOD: Tenascin in nasal polyp tissues from twenty-four polyposis patients and tenascin in inferior turbinates tissues from fifteen chronic hypertrophic rhinitis patients were detected with immunohistochemistry (sp) method. The inferior turbinate mucosa of five healthy volunteers were selected as control. RESULT: Tenascin were expressed in the mucosa epithelial cells and serous cells from nasal polyps and inferior turbinates of chronic hypertrophic rhinitis; The level of tenascin in the mucosa epithelial cells from nasal polyps were significantly(P < 0.01); The level of tenascin in the serous cells from nasal polyps were significantly higher than that in inferior turbinates of chronic hypertrophic rhinitis(P < 0.01); Tenascin were hardly detected in nasal mucosa from healthy volunteers; The tenascin positivity in glandular cell was significantly higher in nasal polyps than in inferior turbinates of chronic hypertrophic rhinitis (P < 0.05). CONCLUSION: There is close relationship between tenascin and nasal polyps. Tenascin is strongly expressed in nasal polyps and its mucosa, where it could be produced by mucosa epithelial cells and serous cells.

Adolescent↗

[Preliminary study of correlation factor in surgery effect of nasal polyps].

OBJECTIVE: To study the relation between nasal polyp pathology, cellular expression of CD45 RO, CD20, CD68, proliferating cell nuclear antigen (PCNA) in nasal polyps and the response to surgery. METHOD: Nasal polyp tissues from 50 patients were evaluated for cellular expression of CD45 RO, CD20, CD68, PCNA using immunohistochemistry SP by counting the average number in 5 chosen high-power fields, histopathological observations were combined with clinic and postoperative dates. Analyses were performed on SPSS10.0. RESULT: Significant correlation was found between CD68+ cells and eosinophils or PCNA positive cells on epithelium. PCNA positive cells on epithelium has significant correlation on fibroblast (P < 0.05). The nasal polyps dominated with CD68+ and high polyp score have significant correlation to cure. CONCLUSION: Extent of inflammatory cells infiltration especially CD68+ or eosinophilia or lymphocytes and polyp score have significant effect on cure rate.

Adolescent↗

Histamine metabolism in nasal polyps.

We attempted to determine the relationship of nasal polyps to histamine (HA) metabolism. Compared to that in allergy-related nasal polyps and infection-related nasal polyps, the level of HA in aspirin-induced asthma-related polyps was significantly lower. Large differences between the groups were not observed in HA-synthesizing enzyme activity, but degradative enzyme activity was much higher in aspirin-induced asthma-related polyps than in other types of nasal polyps tested. These findings suggest the possibility that the amount of HA in polyps associated with aspirin-induced asthma was less because of greatly enhanced degradation. We found, in addition, that in nasal tissues such as polyps, histamine-N-methyl transferase, rather than histaminase, was the principal degradative enzyme.

Amine Oxidase (Copper-Containing)↗

Inducible cyclooxygenase and interleukin 6 gene expressions in nasal polyp fibroblasts: possible implication in the pathogenesis of nasal polyposis.

BACKGROUND: Inflammation is believed to be related to the pathogenesis of nasal polyp (NP). Inducible cyclooxygenase (COX-2) and interleukin (IL) 6 are important mediators of inflammation. However, no information is available regarding the expression of these mediators in nasal polyp fibroblasts (NPFs). The inductive effects of proinflammatory cytokines (IL-1alpha or tumor necrosis factor alpha) alone or in combination with prostaglandin E(2) on IL-6 and COX-2 messenger RNA (mRNA) synthesis in NPFs were investigated. DESIGN: The expressions of IL-6 and COX-2 mRNAs in NPFs and in 34 surgical specimens of NP were detected by Northern blot and in situ hybridization. RESULTS: Significant amounts of constitutive IL-6 and COX-2 mRNAs were produced in NPFs. Cytokines induced IL-6 and COX-2 mRNA synthesis in NPFs. Meloxicam (a specific COX-2 inhibitor) suppressed the induction of cytokines on IL-6 mRNA levels, and these effects could be reversed by exogenous prostaglandin E(2). In situ hybridization revealed that IL-6 and COX-2 mRNAs were detected primarily in fibroblasts, macrophages, and plasma cells. Aggregation of plasma cells as well as collagen deposition in vicinity to IL-6 mRNA-producing fibroblasts was found. Rich vascularity around COX-2 mRNA(+) fibroblasts was also identified. CONCLUSIONS: The pathogenesis of nasal polyposis involves NPFs through synthesizing IL-6 to modulate the activation of immune responses (plasma cell formation) and synthesis of stroma. Inducible cyclooxygenase also contributes to NP development by promoting vasodilatation and modulating the cytokine-induced IL-6 gene expression in NPFs.

Antineoplastic Agents↗

[The expression and relevent study of NO and TNF-alpha in nasal polyp tissue].

OBJECTIVE: To study the expression of NO and TNF-alpha in nasal polyp tissue and explore the effect and relevance of them in the formation of nasal polyp. METHOD: The level of NO and TNF-alpha were measured by RIA and chemical method (Griess Reaction) in nasal polyp tissue, inflammatory mucosa and serum of 33 nasal polyp patients and normal mucosa and serum of 10 deviated septum patients who hospitalized in our hospital from Nov. 1999 to Mar. 2001. RESULT: The level of NO and TNF-alpha in nasal polyp and inflammatory mucosa are higher than that in normal mucosa (P < 0.01). There is significant difference of NO between nasal polyp and inflammatory mucosa (P < 0.01) but not of TNF-alpha (P > 0.05). The level of NO and TNF-alpha in serum of two groups are similar (P > 0.05). There are negative relevance tendency between NO and TNF-alpha in nasal polyp of inflammatory mucosa (r = -0.411, P < 0.02 and r = -0.476, P < 0.01). There is a positive relevance tendency of TNF-alpha between nasal polyp and inflammatory mucosa (r = 0.808, P < 0.01). CONCLUSION: 1. NO and TNF-alpha play important roles in the formation of nasal polyp. 2. There is a negative relevance tendency of NO and TNF-alpha in nasal polyp tissue which reveals the possible negative feedback of NO in the inflammation. 3. The study confirms the theory of microenvironment of nasal polyp and reveals that nasal polyp is separated relatively from and associated closely with the inflammation of nasal cavity.

Adolescent↗

[Detection of glucocorticoid receptor-alpha mRNA expression using FQ-RT-PCR in nasal polyp].

OBJECTIVE: To detect the expression of the glucocorticoid receptor-alpha (GR-alpha) mRNA in nasal polyp and normal nasal mucosa and investigate the significance of GR-alpha in progression of nasal polyp. METHOD: The expression of GR-alpha mRNA in 36 samples of nasal polyp and 31 samples of normal nasal mucosa was examined by using fluorescent quantitative PCR(FQ RT-PCR). RESULT: The GR-alpha mRNA levels in normal nasal mucosa [(135.4 +/- 5.2) x 10(10) copy/g] were significantly higher than those in nasal polyp [(25.5 +/- 5.0) x 10(10) copy/g] (P < 0.01). CONCLUSION: The low expression of GR-alpha mRNA in nasal polyp is related to the progression of nasal polyp.

Adult↗

Vascular endothelial growth factor and children featuring nasal polyps.

BACKGROUND: The aim of this study is to explore the expression of vascular endothelial growth factor within nasal polyps, and the implication of such expression as regards the development of nasal polyps amongst children. MATERIAL AND METHODS: Sixty children suffering from chronic rhinosinusitis were enrolled in this study. Amongst them, 30 patients featured rhinosinusitis with associated nasal polyps. A biopsy specimen was taken from the stalk or the base of the nasal polyp for nasal-polyp sufferers, and the ethmoid sinus for study participants who featured no nasal polyps. The primary lesions biopsied were immunohistochemically stained with a specific endothelial-cell marker and also stained for the presence of vascular endothelial growth factor. The specific level of vascular endothelial growth factor and the mean number of blood vessels present in a visual microscopic (biopsied-specimen) field were calculated under light microscopy (x400). RESULTS: The number of vascular endothelial growth factor-expressing cells for the nasal-polyp group and for the sinusitis group was, respectively, 20.8+/-4.0 and 11.5+/-3.4 per visual field. Correspondingly, the mean intra-polyp blood-vessel density for the nasal-polyp group and that for the control group was, respectively, 10.5+/-2.6 and 5.0+/-1.9 per visual field. The mean intra-polyp blood-vessel density and the number of vascular endothelial growth factor-expressing cells proved to be significantly greater amongst individuals from the nasal-polyp group than was the case for their analogs from the sinusitis group (P<0.01, for both). The presence of vascular endothelial growth factor was found to be distributed predominantly within the vascular endothelium and the mast cells of polyp tissue. In addition, the level of vascular endothelial growth-factor expression and the mean blood-vessel count per field correlated significantly for nasal-polyp tissue (P<0.001). Furthermore, the relative size of nasal polyps correlated significantly with the number of (intra-polyp) vascular endothelial-cell growth factor-expressing cells and the mean blood-vessel density (P<0.05, for both). CONCLUSION: The level of expression of vascular endothelial-cell growth factor (VEGF) and the mean blood-vessel density were shown to be significantly greater within nasal polyps than within corresponding sinusitis mucosa. Clinically, the expression of both of these parameters correlated well with the relative size of nasal polyps. Vascular endothelial growth factor participates in the formation of nasal polyps amongst children suffering from chronic rhinosinusitis (CRS).

Adolescent↗

C-C chemokine ligand 2 gene expression in nasal polyp fibroblasts: possible implication in the pathogenesis of nasal polyposis.

OBJECTIVES: Recruitment of macrophages is essential to the pathogenesis of nasal polyps (NP), since this disease is inflammation-related. In this study, the effects of tumor necrosis factor alpha (TNF-alpha) on the expression of C-C chemokine ligand 2 (CCL2) in fibroblasts derived from nasal polyps (NPFs) were investigated. The roles of cyclooxygenase (COX) 2 and prostaglandins in the mediation of TNF-alpha-stimulated CCL2 gene expression were also investigated. METHODS: Northern blot analysis was used to study the expression of CCL2 and c-Fos in cultured NPFs. An electrophoretic mobility shift assay was used to explore the interactions between activator protein 1 (AP- 1) and DNA. Immunohistochemistry was used to explore the in vivo expressions of COX-2, CCL2, and CD68 in NPs. RESULTS: The Northern blot analysis showed that TNF-alpha stimulated the expression of CCL2 and COX-2 genes, and the synthesis of CCL2 messenger RNA was COX-2-dependent. A transient elevation of c-Fos and c-Jun messenger RNAs was induced by TNF-alpha, whereas COX-2 inhibitors NS-398 and meloxicam abolished the up-regulation of c-Fos. The electrophoretic mobility shift assay revealed that TNF-alpha triggered AP-1 and DNA binding and again, NS-398 and meloxicam inhibited this reaction via reducing c-Fos synthesis. Curcumin (AP-1 inhibitor) markedly suppressed the TNF-alpha-induced CCL2 expression. The immunohistochemical staining of NP surgical specimens also revealed an intimate alignment between CCL2-positive fibroblasts and CD-68-positive macrophages. CONCLUSIONS: These data suggest that NPFs may contribute to NP development by synthesizing CCL2 to promote macrophage recruitment. Furthermore, COX-2 facilitates CCL2 transcription in NPFs via a c-Fos and AP-1 signaling pathway.

Cells, Cultured↗

Expression and distribution of aquaporin-1 in nasal polyps: does it have any significance in edema formation?

BACKGROUND: The aim of this study was to investigate the expression of Aquaporin 1 (AQP1) and AQP4 in polyp tissue. METHODS: Nasal polyps were obtained from 34 patients with nasal polyposis during endoscopic sinus surgery. Bullous middle turbinates with normal-appearing mucosa of 10 patients were used as controls. Expression of AQP1 and AQP4 water channels were determined by immunohistochemical methods. RESULTS: AQP1 has been found to be expressed in fibroblasts located in polyp tissue, especially in the subepithelial area, periphery of seromucous glands, and endothelial cells of venules. CONCLUSION: We have established a high expression of AQP1 water channels in nasal polyp tissue and have suggested two mechanisms to explain this finding. Increased AQP1 expression may be a cause or a consequence of edema formation. Thus, additional studies are needed to elucidate the true mechanism underlying this relationship.

Aquaporin 1↗

[The T-lymphocytes subsets expression in the human recurrent nasal polyps].

OBJECTIVE: To investigate the expression of T-lymphocyte subsets (CD4+, CD8+ and CD45RO+ cells) in human recurrent nasal polyps. METHOD: Nasal polyps tissue samples and peripheral blood were obtained from 17 patients, normal human inferior turbinate mucosa and peripheral blood were obtained as well. Flow cytometry was adopted to detect the expression of surface markers of the T-lymphocytes. All data were analyzed with t-test. RESULT: There were significantly large number of CD4+, and CD45RO+ cells in the tissue of recurrent nasal polyps. The expression percentage of CD3+ CD4+ cells was significantly higher than that of CD3+ CD8+ cells. Ratio of CD3+ CD4+/CD3+ CD8+ was 1.956 +/- 0.093. CONCLUSION: There were generous of T-lymphocytes expression in human recurrent nasal polyps. The ratio of the T-lymphocytes subsets was abnormal high than the usual and this indicated the immunological function were in disorder in the local area. The abnormally higher expression of CD3+ CD4+ cells in the local area may play an important role in the recurrence of human nasal polyps.

Adolescent↗

Prevalence of nasal polyps in adults: the Skövde population-based study.

Patients with nasal polyps present repeatedly in otorhinolaryngology practices, but the prevalence of nasal polyps in the general population is not known. Our objective was to investigate the prevalence of nasal polyps in an adult Swedish population in relation to age, gender, asthma, and aspirin intolerance. A random sample of 1,900 inhabitants over the age of 20 years, stratified for age and gender, was drawn from the municipal population register in Skövde, Sweden, in December 2000. The subjects were called to clinical visits that included questions about rhinitis, asthma, and aspirin intolerance and examination by nasal endoscopy. In total, 1,387 volunteers (73% of the sample) were investigated. The sample size was adequate, with a good fit to the whole population. The prevalence of nasal polyps was 2.7% (95% confidence interval, 1.9-3.5), and polyps were more frequent in men (2.2 to 1), the elderly (5% at > or = 60 years of age), and asthmatics. Subjective symptoms of aspirin intolerance were not found to correlate with polyps. Nasal polyps were more common in adults than was stated by the a priori estimate. The Skövde population-based study is considered representative for the Swedish population.

Adult↗

Inflammatory cells in nasal mucosa and nasal polyps.

OBJECTIVE: Since some controversy exists concerning the frequency of inflammatory cells in nasal polyps, we have compared the frequency of tissue inflammatory cells (lymphocytes, neutrophils, eosinophils and plasma cells) including 11 kinds of lymphocyte subsets in the same specimens of nasal mucosa and nasal polyps. METHODS: Histopathological observations and flow cytometric analyses were performed on eight mucosal specimens of the inferior turbinates of patients with nasal polyps and on 13 polyp specimens. RESULTS: Nasal polyps contained significantly more eosinophils, neutrophils and plasma cells than nasal mucosa, and EG2+ cells (activated eosinophils) were significantly more frequent in nasal polyps than in nasal mucosa. Flow cytometric analysis showed that there were no significant differences in the frequencies of lymphocytes and lymphocyte subsets (CD1+, CD2+, CD3+, CD5+, CD7+, CD4+, CD8+, CD10+, CD19+, CD20+ and HLA-DR+ cells) including CD4/8 ratios between nasal mucosa and polyps, though, both nasal mucosa and polyps contained significantly more lymphocytes than eosinophils, neutrophils or plasma cells. The T cell lineage (CD2+, CD3+, CD5+ and CD7+ cells) was found in high frequency and B cell lineage (CD10+, CD19+ and CD20+ cells) in low frequency in both nasal mucosa and polyps. The frequency of HLA-DR+ cells (most of which were activated T cells) was not significantly different between nasal mucosa and nasal polyps. CONCLUSION: Histopathological and flow cytometric analyses were performed on the composition of inflammatory cells in nasal mucosa of the inferior turbinates and in polyps from the same patients. The elevated numbers of activated eosinophils, neutrophils and plasma cells in nasal polyps compared with nasal mucosa suggest that inflammatory processes play important roles in the pathophysiology of nasal polyps. The frequencies of lymphocytes and lymphocyte subsets were not significantly different between these two tissues.

Adolescent↗

Diffuse mucosal inflammation in nasal polyps and adjacent middle turbinate.

BACKGROUND: Nasal polyp (NP) is the most common mass lesion in the nose with unclear etiology and pathogenesis. OBJECTIVE: To investigate the association of allergy and type of cellular inflammation in Asian patients with NPs. METHODS: Immunohistochemical staining with a panel of antibodies for CD4+ and CD8+ T cells, B cells, Langerhans' cells, eosinophils, neutrophils, and mast cells were performed in pairs of NP tissue and middle turbinate (MT) biopsies from the same side of 48 patients and MT of controls. Serum total IgE and specific IgE to a panel of common local allergens were tested by the UniCAP (Pharmacia & Upjohn AB, Uppsala, Sweden) system. RESULTS: Atopy was found in 29.7% of NP patients. Strong correlations of cell scores were evidenced between the paired samples from nasal polyp patients. The cell patterns in nasal polyp mainly showed a combined cell infiltration with significantly higher CD8+ T cell, eosinophil and neutrophil scores, and an inverse median ratio of CD4+/CD8+ T cells as compared with the MT from controls. CONCLUSION: The similar immunohistochemical pattern of mucosal inflammation in NPs and the paired MT mucosa suggests a diffuse mucosal involvement. This indicates the necessity of anti-inflammatory treatment of changes in the adjacent nasal mucosa in addition to the surgical removal of NPs. Besides the well-recognized eosinophilic inflammation in Caucasian studies, predominant infiltration of T cells, especially CD8+ T cells, could be a key component underlying the pathogeneses of NPs.

Adolescent↗

The replication of influenza A viruses in organ cultures of human nasal polyps.

Organ cultures of human nasal polyps were shown to support the replication of five out of seven human influenza A viruses and three out of six avian strains with varying degrees of efficiency. The ability to replicate was independent of the antigenic formula of the virus. The structure of nasal polyps closely resembled that of normal nasal mucosa and infection with influenza A virus resulted in histological changes analogous to those seen in natural infections. This system provides an in vitro method for more detailed studies of influenza A virus and possibly other respiratory virus infections of man.

Humans↗

Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients.

OBJECTIVE/HYPOTHESIS: Nasal polyposis (NP) is a chronic inflammatory disease of the upper respiratory tract. The pathophysiology is unknown but has been shown to be multifactorial. Free radical-mediated damage has been implicated in the pathogenesis of NP. Superoxide dismutases (SODs) are the first and the most important line of antioxidant enzyme defense against reactive oxygen species. Moreover, isozymes of the SOD family are critical for modulating the activity of nitric oxide, a gaseous free radical that is believed to play roles in the physiology and pathology of respiratory tracts. However, the expression profile of SOD isoforms in NP remains unclear. We aimed to investigate the expression profile of the SOD isoforms in nasal polyps from nonallergic patients. STUDY DESIGN: Prospective study. METHODS: Nasal polyp tissues were obtained from eight nonallergic patients who underwent elective polypectomy; mucosal specimens from the middle turbinates were acquired from eight subjects without NP as control tissues. The expression profile of SOD isoenzymes, SOD1, SOD2, and SOD3, in the nasal tissues was determined by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting (WB). RESULTS: NP in all eight of the NP patients manifested as severe or recurrent sinonasal polyposis clinically. The expression pattern of SOD isoenzymes evaluated by RT-PCR analysis indicated that the mean levels of SOD1 mRNA and, to a greater extent, SOD3 mRNA were higher in polyp tissues than in control tissues. There was no significant difference in the expression levels of SOD2 mRNA between the two groups. The data from ELISA and WB analysis showed that there were increased expressions of SOD1 and SOD3 protein in polyp tissues compared with the control tissues, but there was no difference in the expression of SOD2 protein between the two groups. The results from RT-PCR, ELISA, and WB were paralleled and revealed that the expressions of SOD1 and, to a greater extent, SOD3 were higher in polyp tissues than in the control group. CONCLUSIONS: The expressions of SOD3 and SOD1 were higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP. Our data also suggest that the SODs might be important in the pathogenesis of NP; however, the roles these SOD isoforms, especially SOD3, play in both normal nasal mucosa and NP require further clarification.

Adult↗

Epithelial damage in nasal polyps.

Bronchial epithelial damage occurs regularly in bronchial asthma, but it is not known whether such damage occurs in the mucosa of nasal polyps. We obtained nasal polyp tissues from thirty patients and we examined these tissues for evidence of epithelial damage. Immediately after resection, polyp tissue was fixed in Karnovsky's fixative, embedded in methacrylate and stained with Giemsa pH 6 X 5. Normal nasal tissue from eight patients undergoing nasal septal reconstruction was similarly processed. As a disease control, we examined tissue from eight patients with nasal polyps associated with cystic fibrosis. Tissues were viewed by microscopy and epithelial damage was expressed as the percent of surface involved. Twenty-eight of the thirty patients with idiopathic nasal polyps (93%) showed complete loss of nasal mucosa in varying degrees (range 3-81% of surface; mean, 29%). All patients showed evidence of some epithelial damage, either complete loss or marked desquamation (range 9-99% of surface; mean 54%). In contrast, six of eight biopsies from patients undergoing septal reconstruction and five of eight nasal polyps from patients with cystic fibrosis showed little or no evidence of epithelial damage. The results indicate that nasal polyps regularly show evidence of epithelial damage similar to that seen in bronchial asthma, and this abnormality may partly explain the rhinorrhea which is prominently associated with nasal polyps.

Adult↗

The detection of Mycoplasma pneumoniae in nasal polyps.

The aetiology and microbial flora of nasal polyps is not well understood. No study in the literature has reported an association between the sub-bacterium Mycoplasma pneumoniae and nasal polyps. We have developed an assay method using the Polymerase Chain Reaction (PCR) to amplify a specific region of the M. pneumoniae DNA in extracts of clinical samples using species-specific primers designed to a region of the 16S rRNA. The presence of M. pneumoniae was detected in 13/14 (93%) nasal polyps, in 4/5 (80%) rhinosinusitis mucosal samples but only in 1/7 (14%) of control samples (obstructive turbinates). An epidemic of infections due to M. pneumoniae is expected to occur in 1995. We believe this assay could form the basis of a rapid technique for M. pneumoniae detection. We also propose that the presence of M. pneumoniae may be of importance in the aetiology of nasal polyps.

Blotting, Southern↗