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[Role of ICAM-1 in eosinophilia and prognosis of nasal polyps].

OBJECTIVE: To investigate the role of adhesion molecule ICAM-1 (Intercellular adhesion molecule-1) in eosinophilia and prognosis of nasal polyps. METHOD: Expression of ICAM-1 were detected and quantified in 35 cases of nasal polyps with fluorescence-immunohistochemistry analysis and its relationships to eosinophilia and prognosis of nasal polyps were evaluated. RESULT: The numbers of eosinophils in nasal polyps and control nasal mucosas were 28.4 +/- 10.7/mm2 and 9.9 +/- 8.6/mm2, and fluorescent densities of ICAM-1 were 115.9 +/- 82.4 and 28.2 +/- 17.1. The expression of ICAM-1 was associated with the heaviness of nasal polyps. CONCLUSION: ICAM-1 may play an important role in the formation and prognosis of nasal polyps.

Adult↗

[Expression of prolactin in macrophage of nasal polyps and its significance].

OBJECTIVE: To detect the expression level and distribution of prolactin (PRL) in nasal polyp and to find out the significance of the mechanism of PRL in the invasion of nasal polyp. METHODS: Twenty-five polyp tissues were obtained from the patients who were subjected to nasal polypectomy in our Department. Inferior turbinate mucosa was used as control obtained from 12 patients with rhinogenous snoring. HE staining was performed for routine histopathologic examination. The expression of PRL in nasal polyps was observed by immunohistochemical staining, and six polyp tissues were estimated through double staining for determining cells which expressed PRL. RESULTS: (1) Positive expression of PRL was significantly stronger (t =4.004, P < 0.01) in 25 nasal polyp tissues (2.05 +/- 0.88) than that in 12 normal inferior turbinate mucosa (0.96 +/- 0.50). Positive expression of macrophage (CD68) was significantly stronger (t = 3.519, P < 0.01) in 25 nasal polyp tissues (1.85 +/- 0.83) than that in 12 normal inferior turbinate mucosa (0.93 +/- 0.52). (2) The PRL expressing cell mainly was the macrophage as demonstrated by double immunohistochemical method. CONCLUSION: PRL derived from macrophages of nasal mucosa may participate in the formation of nasal polyp through its local immune modulation.

Adolescent↗

Effect of new macrolide roxithromycin upon nasal polyps associated with chronic sinusitis.

We often observe shrinkage of nasal polyps with low-dose long-term macrolide treatment, which was recently developed in Japan for the treatment of intractable chronic sinusitis. In order to assess the efficacy of this treatment for nasal polyps, we administered the new macrolide roxithromycin (RXM) (1 tablet: 150 mg a day) for at least 8 weeks to 20 patients with nasal polyps associated with chronic sinusitis. It was competent in controlling nasal polyp with the overall incidence of improvement being 52%. The combination of RXM with azelastine (1 mg twice/day), an inhibitor of mediator release, was examined in 20 other patients. It augmented the rate of improvement to 68%, but the increase was not significant. The incidence of improvement increased with time after the start of medication in both groups. Smaller polyps were more likely to decrease in size, but some larger polyps also markedly decreased in size. Associated allergic conditions and the extent of eosinophilic infiltration had no relation to the treatment result. We speculate that the mechanism of effectiveness of RXM is through its suppressive potency in cytokine production from inflammatory cells.

Adult↗

Multiple polysomies in nasal polyps in children.

Karyotyping of a nasal polyp from a 10-year-old girl revealed multiple numerical chromosome changes. Extra copies of chromosome 5, 7, 8, 12, 16, 17, 18, 19, 20, and 21 were present. Only one cytogenetically abnormal nasal polyp of a child has been reported in the literature. The karyotypes of the reported and the present case are remarkably similar. The significance of this finding in a nonneoplastic proliferation is discussed.

Aneuploidy↗

Nasal polyps treatment: medical management.

The objectives of medical management of nasal polyposis are 1) to eliminate nasal polyps and rhinitis symptoms, 2) to reestablish nasal breathing and olfaction, and 3) to prevent recurrence of nasal polyps. Although antibiotics are used for infectious complications of nasal polyposis, only glucocorticosteroids (steroids) have a proven effect on the symptoms and signs of nasal polyps. Topically applied steroids is the therapeutic modality that has been best studied in controlled trials. It reduces rhinitis symptoms, improves nasal breathing, reduces the size of polyps and the recurrence rate, but it has a negligible effect on the sense of smell and on any sinus pathology. Topical steroids can, as long-term therapy, be used alone in mild cases, or combined with systemic steroids/surgery in severe cases. Systemic steroids, which are less well studied, have an effect on all types of symptoms and pathology, including the sense of smell. This type of treatment, which can serve a "medical polypectomy," is only used for short-term improvement due to the risk of adverse effects. Individualized management of nasal polyposis may use long-term topical steroids, short-term systemic steroids, as well as surgery, in various combinations. Exactly how these therapies, which differ in their control of various symptoms, are optimally combined is not yet well established.

Administration, Topical↗

Cultured nasal polyps from nonatopic and atopic patients release RANTES spontaneously and after stimulation with phytohemagglutinin.

BACKGROUND: Eosinophil infiltration of tissue is a hallmark of nasal polyposis in both nonatopic and atopic patients. These cells are thought to play a key role in the nasal polyp inflammatory process. OBJECTIVE: The objective of this study was to investigate whether cultured nasal polyps derived from nonatopic and atopic patients release RANTES both spontaneously and after phytohemagglutinin (PHA) stimulation. METHODS: Nasal polyps were obtained from 12 subjects (6 nonatopic and 6 atopic), cut into 2 to 3 mm large specimens, and cultured for 48 hours with or without PHA. RANTES was measured in the culture supernatant by ELISA (R&D Systems, U.K.). RESULTS: Immunoreactive RANTES was found to be present in the culture supernatant of nasal polyps derived from both nonatopic and atopic patients with no difference between the two groups (median: 3.8 vs 2.9 pg/mg/ml). On incubation with PHA, nasal polyps from both nonatopic and atopic patients released sevenfold and 11-fold greater amounts of RANTES than unstimulated samples. As determined by immunohistochemistry, RANTES was localized to the vascular endothelium in nasal polyps from both groups of patients. CONCLUSIONS: This study demonstrates that cultured nasal polyps derived from both nonatopic and atopic patients release RANTES spontaneously and after PHA stimulation. This observation and the finding that RANTES is present in nasal polyp endothelial cells suggest that this chemokine may be an important mediator of eosinophil and lymphocyte recruitment in both nonatopic and atopic nasal polyposis.

Adult↗

Expression and distribution of ion transport mRNAs in human nasal mucosa and nasal polyps.

CONCLUSIONS: Our results indicate that the electrogenic kidney Na(+)/HCO(3)(-) cotransporter (kNBC), KCl cotransporter (KCC1 and -4) and Ca(2+)-activated Cl(-) channel (CaCC1, -2, -3) mRNAs are expressed in normal nasal mucosa and nasal polyp, suggesting that altered expression of all CaCC mRNAs in nasal polyp may cause impaired electrolyte and water transport across the epithelial cells. OBJECTIVE: Electrolyte transport by nasal epithelia has been suggested to be important for controlling the quantity and composition of the nasal fluid and may play an important role in the development of nasal polyps. Transepithelial transport of ions and water in various fluid-transporting epithelia is strictly dependent on the localization of specific membrane proteins in the polarized epithelial cells. In this study we investigated the expression and distribution of mRNA transcripts for kNBC, pancreatic NBC, KCC1, -2, -3, -4 and CaCC1, -2, -3 gene families in human nasal mucosa and nasal polyp. MATERIAL AND METHODS: The expression and localization of these gene families were investigated in inferior turbinate tissues and nasal polyp using reverse transcriptase polymerase chain reaction (RT-PCR), semiquantitative RT-PCR and in situ hybridization. RESULTS: mRNAs for kNBC, KCC1 and -4 and all the CaCC families (CaCC1, -2 and -3) are expressed in human turbinate mucosa and nasal polyp. The expression levels of kNBC and KCC1 and -4 mRNAs did not differ between nasal mucosa and nasal polyp. However, the expression levels of all the CaCC genes were significantly decreased in nasal polyp. In situ hybridization revealed that the expression of these genes was mainly localized in the epithelial layer and submucosal glands of inferior turbinate mucosa and in the epithelial layer of nasal polyp.

Adult↗

High levels of nitric oxide synthase activity are associated with nasal polyp tissue from aspirin-sensitive asthmatics.

The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N(G)-nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72+/-220.79; B, 23.71+/-41.06; and C, 549.71+/-132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity (p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.

Adult↗

[Expression and significance of vascular permeability factor in nasal polyps].

OBJECTIVE: To study the expression and significance of vascular permeability factor(VPF) in nasal polyps. METHODS: Expression of VPF and its receptor flk-1 in nasal polyps from 9 patients and inferior turbinates from 8 patients with chronic rhinitis were prospectively studied with immunohistochemistry. Each tissue section was observed under optical microscope. RESULTS: The VPF positivity in vascular endothelium and in gland cell was significantly higher in nasal polyps than in inferior turbinates (P < 0.01 and P < 0.05, respectively). The flk-1 labeling index of vascular endothelium was significantly higher in nasal polyps than that in inferior turbinates (P < 0.01). CONCLUSION: VPF may play a key role in the formation of heavy edema of nasal polyps.

Adult↗

Extracellular signal-regulated kinase is involved in tumor necrosis factor-alpha-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells.

OBJECTIVES: Mucus secretion and inflammatory cytokines are increased in cases of chronic sinusitis with polyp. In this study we initially investigated the localization of MUC5AC protein in human nasal polyps. We then examined whether tumor necrosis factor-alpha (TNF-alpha) induces MUC5AC gene expression and whether extracellular signal-regulated kinase (ERK) plays a role in TNF-alpha-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. Finally, we investigated whether MUC5AC and activated ERK are co-expressed in goblet cells. MATERIAL AND METHODS: Human nasal polyp epithelial cells were isolated and subcultured. Passage-2 polyp epithelial cells were treated with 10 ng/ml TNF-alpha. ERK involvement was determined by Western blotting and MUC5AC gene expression by reverse transcriptase polymerase chain reaction. An ERK kinase assay and an inhibitor study using PD98059 were also performed. Immunohistochemical staining using polyclonal MUC5AC antibody and a phospho-specific ERK antibody was done in nasal polyps. RESULTS: MUC5AC was found to be expressed in the majority of goblet cells in human nasal polyp epithelium. TNF-alpha induced MUC5AC gene expression, and ERK activation was found to be essential for TNF-alpha-induced MUC5AC gene expression in cultured human nasal polyp epithelial cells. In addition, both MUC5AC and activated ERK were co-expressed in goblet cells of human nasal polyp epithelium. CONCLUSIONS: TNF-alpha induces MUC5AC gene expression via ERK in cultured human nasal polyp epithelial cells.

Blotting, Western↗

[Ultrastructure of mast cells in nasal polyps].

More mast cells were found in the base of nasal polyps and most of them showed varying degrees of degranulation. There were three types of granules in the cytoplasm, namely: high electron-dense granules with crystalline structure; low electron-dense granules with netlike structure and some granules containing a mixture of components of different electron density. The appearance of cell degeneration in nasal polyps and granules broken away from mast cells through the dissolved cellular membrane were noted. These findings suggested that mast cells degranulation in nasal polyps might be in some way different from the more rapid changes found in cells activated by the classical IgE-mediated pathway and showed that mast cell degranulation may play a part in formation and growth of the nasal polyps.

Cell Degranulation↗

Ultrastructural findings of capillaries in nasal polyps.

The permeability of capillaries in nasal polyps is very high. The continuous capillary is the typical type but the discontinuous type and fenestrated type are also observed. These fenestrated capillaries are found near the stalk region. Although discontinuous capillaries undoubtedly have high permeability, many morphological findings which show this high permeability are observed even if they are continuous capillaries. There are many endothelial projections into the capillary lumen, well-developed marginal folds and pinocytotic vesicles. The endothelial projections complicatedly agglutinate to another part of the endothelium or projections and sometimes form the reticulation. Morphological findings inhibiting the interstitial oedema are also observed. Several layers of basement membrane appear around the capillaries, endothelial projections into the interstitium and the formation of the appositional junction between the pericytes and endothelium. Well-developed basement membrane inhibits the leakage of large molecules. The large spaces which are enclosed by external projections demonstrate the efficient absorption of interstitial fluid. The external projections and the formation of the appositional junction between pericyte and endothelium may support the findings of the rebirth capillaries. The capillaries in nasal polyps are very small in number. If the capillaries or venules were quickly created the interstitial fluid would be efficiently absorbed in the vessels.

Adult↗

[Expression of Th1, Th2-typed cytokines and its significance in nasal polyps].

OBJECTIVE: To evaluate the possible role of cytokines in pathophysiology and treatment of nasal polyps. METHOD: The expressions of Th1-typed cytokines IFN-gamma, IL-2, IL-12 and Th2-typed cytokines IL-4, IL-5, IL-8, IL-10, IL-13 were investigated with enzyme-linked immune sorbent assay(ELISA) in 25 patients with nasal polyps. RESULT: There was a significant upregulation of Th2-typed cytokines IL-4, IL-5, IL-8, IL-10, IL-13 in nasal polyps compared with normal nasal mucosa, especially IL-4 and IL-5 (3.9 times and 8.8 times higher than normal mucous respectively) while the expression of Th1-typed cytokines IFN-gamma, IL-2, IL-12 decreased after treated with local glucocorticoid. The levels of Th2-typed cytokines decreased significantly and Th1-typed cytokines had no obvious change. CONCLUSION: The upregulation of Th2-typed cytokines such as IL-4, IL-5, IL-8, IL-10, IL-12 may play an important role in the pathophysiology of nasal polyps and Th2-typed cytokines can be viewed as a target of treatment to nasal polyps.

Adolescent↗

[The effect of fungi in the pathogenesis of nasal polyps and chronic rhinosinusitis].

OBJECTIVE: To study the effect of fungi in the pathogenesis of nasal polyps and chronic rhinosinusitis (CRS). METHOD: This study were divided two groups, the first was the experimental group: Nasal mucus membrane and nasal polyps were collected from patients with CRS (with and without polyps), and the second was the control group, nasal mucus were collected from OHc. Fungal-specific PCR were performed on each sample. The anther was used 0.9% sol sodium chloride to wash the autopsy tissues 5 times, and then PCR analysis was performed. chi-squared analysis was used to test for statistical difference between these groups. RESULT: PCR technique detected fungal DNA were 89.2% and 89.4% in nasal polyps and nasal mucous membrane respectively, and 66.7% in normal control subjective. There were statistically significant difference in these groups. After using 0.9% sol sodium chloride to wash the autopsy tissues, the fungi's positive rate was dropped. CONCLUSION: Fungi was important in the pathogenesis of nasal polyps and CRS.

Adolescent↗

[T-lymphocyte subsets and inflammatory cytokines of interleukin-5 and interleukin-10 expression in human nasal polyp tissue].

OBJECTIVE: To investigate the distribution of T-lymphocyte subsets (CD4+ and CD8+ cells) and the expression of IL-5 and IL-10 protein-positive cells in nasal polyps. METHODS: The specimens of thirty-two nasal polyps and six control subjects were studied by Immunohistochemical method to detect CD4+, CD8+, IL-5+ and IL-10+ cells. A mean numbers of positive cells per high power field (10 x 40) were counted. All data were analyzed with t-test and correl-test. RESULTS: There were significantly large number of CD4+ and CD8+ cells in nasal polyps (P < 0.001). A significant predominance of CD4+ cells over CD8+ cells was found in the two subgroups (subepithelia, arounding glands and blood vessels) of nasal polyp (P < 0.001). There were an abundant number of IL-5+ IL-10+ cells, whereas significantly difference higher concentrations than that in the controls (P < 0.001). IL-5+ cells were more than IL-10+ cells in nasal polyps (P < 0.05), and most of IL-5+ cells were plasmacytes and lymphocytes. There was a significant correlation between the counts of CD4+/CD8+ and IL-5+/IL-10+ in the subgroup of nasal polyps arounding glands and blood vessels (r = 0.78, P < 0.01). CONCLUSIONS: This study indicated that CD4+ T-lymphocytes and IL-5 high expression may play an important role in the nasal polyps. Migration of plasmacytes and lymphocytes in polyps may participate in the inflammatory reaction. The disturbance of cellular and humoral immunity and imbalance of cytokines distribution may play a crucial role in the pathogenesis of nasal polyps.

Adult↗

[Expressions of cystic fibrosis transmembrane conductance regulator in epithelial cells of nasal polyps and normal turbinate mucosae].

OBJECTIVE: To investigate the role of cystic fibrosis transmembrane conductance regulator (CFTR) in human nasal polyps. METHOD: CFTR were studied in 28 cases of nasal polyps and 7 cases of normal turbinate mucosae with immunochemistry staining. RESULT: (1) CFTR was detected in the two tissues and localized mainly in epithelial cells and secretory cells. Its staining showed a more prominent feature in nasal polyps than in normal turbinate mucosae. CFTR showed a typical apical distribution in the normal turbinate mucosae whereas, in the nasal polyps, CFTR demonstrated the other pattern of localization comprising cytoplasmic distribution and typical apical location. (2) Both the CFTR staining intensity of apical and cytoplasmic distribution in the epithelial cell layer from nasal polyps were higher than those from turbinates (P < 0.05, P < 0.05 respectively). CONCLUSION: Over expression and dysfunction of the chloride channels CFTR may play a role in the formation of nasal polyps.

Adolescent↗

Arachidonic acid metabolites in human nasal polyps.

Arachidonic acid metabolites (AAMs) are known to be involved in inflammation. It is suggested that AAMs play an important role in the pathogenesis of nasal polyp. We have measured the levels of prostaglandin E2, 6-keto prostaglandin F1 alpha, thromboxane B2, leukotriene B4 and a mixture of leukotriene C4, D4 and E4 in both nasal polyp and maxillary sinus mucosa by radioimmunoassay. Our results showed that arachidonic acid metabolism in nasal polyps from allergic patients was more active than that from non-allergic patients. The arachidonic acid metabolism in nasal polyp was more active than in maxillary sinus mucosa among allergic patients. On the other hand, arachidonic acid metabolism in maxillary sinus mucosa was more active than that in nasal polyps among non-allergic patients. On the basis of these results, we hypothesized the causal mechanisms of nasal polyps as follows: The nasal polyp in allergic patients is caused by primary inflammation of the nasal mucosa, and sinusitis occurs secondarily. In non-allergic patients, the primary side of inflammation is located in the maxillary sinus mucosa, leading to the secondary formation of nasal polyp.

6-Ketoprostaglandin F1 alpha↗