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Nasal Tissues (nasal + tissue)
Selected AbstractsA Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] Differential expression of the interleukin 5 receptor , isoforms in blood and tissue eosinophils of nasal polyp patientsALLERGY, Issue 5 2009P. Gevaert Background:, Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5R,) isoform, or a secreted (SOL IL-5R,) isoform, on both protein and transcript level in vitro and in vivo. Methods:, A real-time PCR, FACS and ELISA were established to determine IL-5R, isoform expression in peripheral blood and nasal tissue from control subjects and nasal polyp (NP) patients with or without asthma. Human peripheral blood eosinophils were incubated with IL-5 and were analyzed for SOL-IL-5R, and TM-IL-5R, mRNA and protein levels in comparison with CD-69 expression. Results:, SOL-IL-5R, and TM-IL-5R, mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5R, expression correlated to disease severity and eosinophils counts, whereas TM-IL-5R, levels were inversely correlated to eosinophils counts and SOL-IL-5R, expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5R, expression in NP tissue eosinophils vs blood eosinophils. Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down-regulation of TM-IL-5R, after 2 and 24 h. Conclusion:, The expression of SOL-IL-5R, and TM-IL-5R, differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5 reduces their responsiveness to IL-5 by regulated expression of the IL-5R, isoforms. Since, TM-IL-5R, is down-regulated and SOL-IL-5R, (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans. [source] Role of Local Immunoglobulin E Specific for Alternaria alternata in the Pathogenesis of Nasal Polyposis,THE LARYNGOSCOPE, Issue 1 2008Albert Sabirov MD Abstract Objective/Hypothesis: The role of fungal pathogens in the etiology of nasal polyposis remains unclear. The aim of this study was to determine whether there was a correlation between the presence of Alternaria -specific immunoglobulin (Ig)E antibodies, eosinophilic inflammation, and the development of nasal polyps. Study Design: Prospective study. Methods: Serum and nasal tissue homogenates from 21 patients with manifestations of chronic sinusitis with nasal polyps were compared with specimens from 13 chronic sinusitis patients without polyps and 8 healthy controls. The Phadia ImmunoCAP and enzyme-linked immunosorbent assay were used to quantify levels of total IgE and Alternaria -specific (IgE, IgG, and IgA) antibodies. Eosinophil cationic protein (ECP) and tryptase levels were measured in tissue homogenates, whereas the inflammatory response was evaluated using tissue eosinophil counts in tissue samples. Results: Serum analysis revealed no difference in the levels of total IgE and Alternaria -specific IgE, IgG, and IgA antibodies between the study groups. In contrast, the levels of Alternaria -specific IgE in tissue with polyps were significantly higher than in nonpolyp tissue. Increases in total tissue IgE paralleled increased levels of Alternaria -specific IgG and IgA antibodies in chronic sinusitis with nasal polyps as compared with control groups. A positive correlation was found between Alternaria -specific IgE and ECP in tissue. Increased mean levels of ECP corresponded to increased eosinophil counts in the group of patients with polyps. Conclusions:Alternaria -specific IgE and eosinophilic inflammation in nasal tissue correlates with the incidence of nasal polyps irrespective of specific IgE antibodies in serum. Together, the correlation between the local immune responses and the eosinophilic inflammation in nasal polyps suggests a possible role of Alternaria in the pathogenesis of nasal polyposis. [source] Neutrophil-Derived Metalloproteinase-9 Predicts Healing Quality after Sinus Surgery,THE LARYNGOSCOPE, Issue 1 2005J B. Watelet MD Abstract Background: In a recent study, we have shown that gelatinase-B (metalloproteinase [MMP]-9) in nasal secretions can have both monitoring and predictive value on the healing outcome after functional endoscopic sinus surgery (FESS) to treat chronic rhinosinusitis (CRS) and nasal polyposis (NP). In this work, we aimed to explore the source of MMP-9 and the influence of inflammation on MMP-9 expression and release in nasal tissue and secretions during airway remodelling after surgery. Methods: Biopsies from 23 patients operated by FESS for CRS or NP were collected 1, 3, and 6 months after sinus surgery. MMP-9 expression in the paranasal mucosa was correlated with healing quality, with MMP-9 concentrations in nasal fluid, and with histomorphologic findings (edema, fibrosis, ,smooth muscle actin, CD-68, myeloperoxidase, EG2, and transforming growth factor [TGF]-,1 stainings). Results: MMP-9 concentrations in nasal fluid were paralleled by MMP-9 expression inside the extracellular matrix (ECM) after sinus surgery. MMP-9 expression in ECM was significantly correlated with healing quality (r = 0.378, P = .0181), and poor healers presented significantly more edema (P < .05). The amounts of MMP-9 in nasal fluid were significantly and independently predicted by the number of neutrophils (P = .0224) and macrophages (P = .0497) in the tissue. In contrast, MMP-9 expression was not related to fibrosis, number of myofibroblasts, or TGF-,1 expression in ECM. Conclusions: MMP-9 expression is increased in the ECM during wound healing and parallels concentrations of MMP-9 in nasal fluids. Inflammatory cells represent the major source of increased MMP-9 expression, which is linked to poor healing quality. [source] Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitisCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2006M. Peters-Golden Summary Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists. [source] Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polypALLERGY, Issue 1 2009D. H. Han Background:, Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. Methods:, BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund,Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. Results:, Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund,Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/,l (sensitivity 70%, specificity 70%). Conclusion:, Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count , 300 cells/,l may be predictive factors for BHR in patients with CRSNP. [source] Inverse Association between T-Cell Immunoglobulin and Mucin Domain-1 and T-bet in a Mouse Model of Allergic Rhinitis,THE LARYNGOSCOPE, Issue 6 2007Geng Xu MD Abstract Background: It has been suggested that human hepatitis A virus cellular receptor, also known as T-cell immunoglobulin and mucin domain-1 (TIM-1), plays an important role in the development of allergic diseases on the basis of epidemiologic data, but the molecular mechanism has been unclear. In a murine model of ovalbumin (OVA)-sensitized allergic rhinitis (AR), we examined the expression of TIM-1 and its correlation with T helper1-associated transcription factor, T-bet, as a potential mediator of T-cell immunoglobulin expression. Methods: Mice were challenged intranasally with OVA to elicit AR. The expression of TIM-1 in nasal tissues was examined by real-time reverse-transcription polymerase chain reaction (RT-PCR), and the surface expression of TIM-1 in peripheral blood mononuclear cells was evaluated by means of flow cytometry. In addition, the expression of TIM-1 as well as T-bet in splenic lymphocytes was examined by Western blotting. Results: TIM-1 mRNA was increased significantly in nasal tissues (P < .05) as seen by real-time RT-PCR. Flow cytometry indicated a differential TIM-1 expression of 135.5 ± 34.2 in the AR group versus 51.1 ± 10.9 in the control group (P < .05). The mean values of normalized TIM-1 were 0.43 ± 0.18 and 0.21 ± 0.10 in AR and control groups, respectively, whereas the mean values of normalized T-bet were 0.22 ± 0.13 and 0.67 ± 0.17 in the AR and control groups, respectively. There was a significant difference in the production of TIM-1 as well as T-bet in AR mice versus control mice (P < .05). The increased production of TIM-1 correlated significantly with the decreased T-bet in spleen tissue of AR mice (r = ,0.52, P < .05). Conclusion: Our experimental model recapitulates an increase in lymphocyte TIM-1 expression seen in AR both locally and systemically. Our results also demonstrate an inverse relationship between lymphocyte TIM-1 and T-bet expression, suggesting a possible mechanism that TIM-1 influences the development of AR. [source] A Possible Role of CD4+CD25+ T Cells as Well as Transcription Factor Foxp3 in the Dysregulation of Allergic RhinitisTHE LARYNGOSCOPE, Issue 5 2007Geng Xu MD Abstract Background: Allergic rhinitis (AR) is a Th2 predominant disease, and its pathogenic mechanism is still poorly understood. CD4+CD25+ T cells account for approximately 5% to 10% peripheral CD4+ T cells and has been shown to regulate the activation of effector T cells in the periphery. The activity of CD4+CD25+ T cells is associated with the transcription factor Foxp3. The present study aimed to evaluate the possible role of CD4+CD25+ T cells as well as Foxp3 in the pathogenesis of AR. Methods: Nasal tissues and peripheral blood mononuclear cells (PBMCs) were obtained from 17 patients with AR and 11 control subjects. Foxp3 was detected in nasal tissues by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR). CD4+CD25+ T cells and Foxp3 were evaluated in PBMCs by using flow cytometry. Concentrations of interleukin-2 (IL-2) and interferon-, (IFN-,) were measured by enzyme-linked immunosorbent assay (ELISA) in cultured PBMCs in the presence or absence of stimulation with phorbol ester (PMA) and Ionomycin. Results: The numbers of Foxp3+ cells was 129.5 ± 35.6 and 44.2 ± 20.5 cells/mm2 in nasal mucosa of two groups (P < .05). There were less Foxp3+ lymphocytes and decreased Foxp3 mRNA in AR compared with the control (P < .05). The frequencies of the CD4+CD25+ population in PBMCs of two groups were 1.99 ± 0.95% and 3.55 ± 1.27% (P < .05). There was significant difference in the frequencies of the Foxp3+CD4+ CD25+ population (1.81 ± 0.77 vs 3.37 ± 1.04, P < .05) and mean fluorescence intensity (MFI) of Foxp3 (5.93 ± 2.64 vs 11.72 ± 4.29, P < .05) in PBMCs of two groups. After stimulation, the concentrations of IL-2 and IFN-, were 182.72 ± 85.11 pg/mL and 348.94 ± 151.88 pg/mL in PBMCs with AR, while those were 90.6 ± 61.5 pg/mL and 155.64 ± 68.33 pg/mL in controls (P < .05). Conclusion: Our results indicate that CD4+ CD25+ regulatory T cells as well as Foxp3 may play a crucial role in immunological imbalance of AR. These findings suggest that increasing Foxp3 and CD4+CD25+ T cells have the potential to be new therapeutic targets for the treatment of AR. [source] Heme Oxygenase (HO)-1 Is Upregulated in the Nasal Mucosa With Allergic Rhinitis,THE LARYNGOSCOPE, Issue 3 2006Ahmed Elhini MD Abstract Background: Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. Three isoforms of HO have been discovered. Recently, HO-1 has been found to be upregulated after allergic inflammations of the lower airway. Objective: The objective of this study was to address the expression of HO isoenzymes 1 and 2 in the nasal mucosa of patients with allergic rhinitis as well as normal control subjects. Methods: Nasal mucosa from 30 patients with persistent allergic rhinitis as well as from 10 normal volunteers was used in this study. We used immunofluorescent technique, Western blotting, and real-time quantitative polymerase chain reaction to localize and quantify the expression of these isoenzymes in normal and allergic human nasal tissues. Results: We found that HO-1 is expressed in the epithelial cells of seromucinous glands and macrophages with significant upregulation of its glandular expression in allergic rhinitis but with no difference in its macrophage expression between the study groups in contrast to HO-2 that is expressed in the vascular endothelial lining cells as well as macrophages with no marked difference between the study groups. Conclusion: We demonstrated that expression of HO-1, but not HO-2, was upregulated within the nasal tissues in allergic rhinitis inflammation, and understanding the induction of HO-1 expression may provide for better management of allergic rhinitis that involves oxidative stress. [source] | ||||||||||