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Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese

BACKGROUND Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. OBJECTIVE To investigate the immunopathologic profiles of CRSwNP and CRSsNP in adult Chinese. METHODS Histologic characteristics of surgical samples were analyzed in 50 controls, 94 CRSsNP patients, and 151 CRSwNP patients. Tissue samples from 17 controls, 36 CRSsNP patients, and 45 CRSwNP patients were stained for CD3, CD4, CD8, CD20, CD68, myeloperoxidase, and dendritic cell lysosome-associated membrane protein. Expression profiles of transcription factors of T-cell subsets in relation to cytokines and a marker of natural killer T cell (Valpha24) were examined by means of quantitative RT-PCR. RESULTS Over half of CRSwNP patients presented noneosinophilic inflammation. CRSwNP had a higher number of eosinophils, plasma cells, and CD3(+), CD8(+), CD20(+), and CD68(+) cells and a lower myeloperoxidase expression rate than CRSsNP. Expression levels of transcription factors and cytokines of T(H)1/T(H)2/T(H)17 were increased, whereas the expression rate of Forkhead box p3 and TGF-beta1 was decreased in both CRSsNP and CRSwNP compared with controls. Comparing CRSsNP and CRSwNP, CRSsNP had higher levels of IFN-gamma expression, whereas only eosinophilic CRSwNP demonstrated an enhanced expression of GATA-3 and IL-5. Compared with noneosinophilic CRSwNP, an exaggerated T(H)2/T(H)17 reaction and Valpha24 expression were found in eosinophilic CRSwNP. CONCLUSION Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced T(H)1/T(H)2/T(H)17 responses. CRSsNP is confirmed to be a predominant T(H)1 milieu, whereas T(H)2 skewed inflammation with predominant T(H)17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.

Expression of osteopontin in chronic rhinosinusitis with and without nasal polyps

Background:  Osteopontin (OPN) is a multifunctional 34‐kDa extracellular matrix protein that can influence the inflammatory process. However, the presence of OPN in human sinonasal mucosa and its roles in the inflammatory process of chronic rhinosinusitis (CRS) are not clear. This study investigated the expression of OPN in human sinonasal mucosa, its cytokine‐driven expression regulation, and its effect on cytokine production in sinonasal mucosa.

Chronic rhinosinusitis with and without nasal polyps is associated with decreased expression of glucocorticoid-induced leucine zipper

Background Chronic rhinosinusitis without nasal polyps (CRSsNP) and with nasal polyps (CRSwNP) is characterized by persistent inflammation of sinonasal mucosa. Glucocorticoid‐induced leucine zipper (GILZ) is a recently described anti‐inflammatory mediator.

Histological and immunological observations of bacterial and allergic chronic rhinosinusitis in the mouse

Background The purpose of this study was to elucidate histological and immunologic features of mouse models of bacterial chronic rhinosinusitis (BCRS) and allergic chronic rhinosinusitis (ACRS). Methods A BCRS mouse model was established using Streptococcus pneumoniae inoculation plus Merocel (Medtronic, Jacksonville, FL) ostiomeatal obstruction for 12 weeks. An ACRS mouse model was developed by means of ovalbumin (OVA) i.p. injection and subsequent repeated OVA intranasal challenge for 12 weeks. Histological changes of sinonasal mucosa of both models were examined by means of hematoxylin and eosin staining for general morphology and inflammatory cell, periodic acid-Schiff staining for goblet cell, and Masson-trichrome staining for collagen. Enzyme-linked immunosorbent assay was used to detect the concentrations of various cytokines in nasal lavage fluid. Results Polymorphonuclear neutrophil infiltration in lamina propria was more obvious in the BCRS model, whereas eosinophil infiltration was more apparent in the ACRS model. Significant goblet cell and subepithelial gland hyperplasia, subepithelial fibrosis, epithelial thickening, and mononuclear cell infiltration were shown in both models with more severe extent found in the ACRS model. Interleukin (IL)-6 and tumor necrosis factor alpha levels in NLF from both models were increased and peaked at 1 week. Interferon gamma levels were also up-regulated in both models but reached maximum at 1 week in the BCRS model and 4 weeks in the ACRS model. IL-8 (CXCL8) levels were only increased in BCRS mice and peaked at 1 week, whereas IL-5, IL-13, and eotaxin (CCL11) levels were only enhanced in ACRS mice and peaked at 1 week. The Th1/Th2 ratio in BCRS mice was significantly higher than that in ACRS mice (6.68 ± 2.33 versus 1.37 ± 0.86; p < 0.01). Conclusion Histological and immunologic features of BCRS and ACRS mouse models were similar to those of human noneosinophilic and eosinophilic CRS, respectively. BCRS and ACRS mouse models have distinct immunologic characteristics and are applicable for CRS research.

Group II subfamily secretory phospholipase A2 enzymes : expression in chronic rhinosinusitis with and without nasal polyps

Background:  Group II subfamily secretory phospholipases A2 (sPLA2s) are the enzymes that can play a major role in inflammation. However, the presence of group II subfamily sPLA2s in human sinonasal mucosa and their roles in chronic rhinosinusitis (CRS) are not well known. The purpose of this study was to investigate the expression of group II subfamily sPLA2s in human sinonasal mucosa from controls and CRS patients with and without nasal polyps (NPs) and the regulation of expression by proinflammatory cytokines.

The cytokine-driven regulation of secretoglobins in normal human upper airway and their expression, particularly that of uteroglobin-related protein 1, in chronic rhinosinusitis

BackgroundThe involvement of secretoglobins (SCGBs) other than SCGB1A1 (Clara cell 10-kDa protein, CC10) in human airway diseases remains unexplored. Among those SCGBs, SCGB3A2 (uteroglobin-related protein 1, UGRP1) is particularly interesting, given its structure and function similarities with SCGB1A1 (CC10). The aim of this study was to investigate the expression regulation of SCGBs other than SCGB1A1 (CC10) in human upper airway, and their potential involvement, particularly that of SCGB3A2 (UGRP1), in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP).MethodsEight SCGB family members including SCGB3A2 (UGRP1), SCGB1C1 (ligand binding protein RYD5), SCGB1D1 (lipophilin A), SCGB1D2 (lipophilin B), SCGB1D4 (interferon-γ inducible SCGB), SCGB2A1 (mammaglobin 2), SCGB2A2 (mammaglobin 1), and SCGB3A1 (uteroglobin-related protein 2) were studied. The regulation of SCGBs mRNA expression in normal nasal mucosa by proinflammatory, Th1, and Th2 cytokines was studied through nasal explant culture. SCGBs mRNA expression levels in CRSsNP and CRSwNP patients and controls were compared. The mRNA levels were detected by means of quantitative reverse transcriptase-polymerase chain reaction. The protein expression of SCGB3A2 (UGRP1) was analyzed using immunohistochemistry.ResultsThe expression of SCGBs except SCGB1D2 (lipophilin B) could be found in upper airway and be differentially regulated by different cytokines. SCGB3A2 (UGRP1) mRNA expression was induced by Th1 cytokine, but suppressed by proinflammatory and Th2 cytokines. SCGBs mRNA expression was altered in CRS; particularly, SCGB3A2 (UGRP1) protein and mRNA expression was markedly decreased in both CRSsNP and CRSwNP and its protein levels inversely correlated with the number of total infiltrating cells, preoperative sinonasal CT scores, and postoperative endoscopy and symptom scores.ConclusionSCGBs except SCGB1D2 (lipophilin B) are expressed in human upper airway and their expression can be differentially regulated by inflammatory cytokines. SCGBs mRNA expression is altered in CRS. Reduced production of UGRP1, which is likely due, at least in part, to a local cytokine environment, may contribute to the hyper-inflammation in CRS and correlates with response to surgery.

Lack of association of Clara cell 10-kDa protein gene variant with chronic rhinosinusitis in a Chinese Han population.

Background Clara cell 10-kDa protein (CC10) is an anti-inflammatory molecule and has been implicated in the involvement of the pathogenesis of asthma and chronic rhinosinusitis (CRS). A single nucleotide polymorphism (SNP) in CC10 gene (A + 38G) was previously shown to be associated with asthma and plasma CC10 levels. The purpose of this study is to examine whether there is an association between the CC10 A + 38G SNP, plasma CC10 levels, and CRS in a central Chinese population of Han nationality. Methods The CC10 A + 38G SNP was analyzed by means of polymerase chain reaction with restriction fragment length polymorphism and plasma CC10 levels were measured using enzyme-linked immunosorbent assay in 220 patients with CRS (90 patients with nasal polyps [NPs] and 130 patients without NPs) and 180 healthy control subjects. Among 220 patients with CRS, 108 patients were atopic subjects. Severity of disease was determined by coronal computed tomography (CT) scan in CRS patients, which was graded according to Lund and Mackay. Results The frequency of the A allele was 0.394, which was not significantly higher than the frequencies of other reported ethnic groups except for German. No association between the CC10 A + 38G SNP and CRS, any subgroup of CRS, or CRS severity could be found. Although subjects carrying the AA genotype had a significantly lower plasma CC10 concentration than those carrying the GG and GA genotypes in both CRS and control groups (p = 0.00 for all), no association was found between the plasma CC10 levels and CRS phenotype. Conclusion The CC10 A + 38G SNP may not exert a substantial influence on the development of CRS in the Chinese Han population.

Expression of tenascin and fibronectin in nasal polyps

SummaryTo explore the role of tenascin (TN) and fibronectin (FN) in the pathophysiology of nasal polyps (NP), the expression of TN and FN in NP from 34 patients and inferior turbinates from 20 patients with deviation of nasal septum was immunohistochemically studied. In patients with NP, the relations between expression and histopathological features, eosinophils (EOS) infiltration, clinical staging and the size of NP were analyzed. Our study showed that the gray score of TN and FN expression was 163.10±10.54 and 163.24±11.52 in NP respectively, whereas it was 175.49±9.29 and 173.93±7.92 in inferior turbinates respectively. The difference between two groups was significant (P<0.01). The expression of TN and FN in edematous type was significantly stronger than that in cystic and glandular type and fibrous type (P<0.05). The association between FN expression and EOS infiltration was significant (r=−0.60,P<0.01). The expression of TN and FN did not correlate with clinical staging and size (P>0.05). It was suggested that abnormal ECM might contribute to proliferation of epithelia, accumulation of EOS and edema formation, thereby causing development of NP.OBJECTIVE To explore the role of tenascin (TN) and fibronectin (FN) in the pathophysiology of nasal polyp. METHODS The expression of TN and FN in nasal polyps from 34 patients and in inferior turbinates from 20 patients with deviation of nasal septum was studied with immunohistochemical method. In patients with nasal polyps, the relations between expression and histopathologic characteristics, eosinophilias (EOS) infiltration, clinical staging and the size of nasal polyps were analyzed. RESULTS (1) The gray score of TN and FN expression was 163.10 +/- 10.54 and 163.24 +/- 11.52 in nasal polyps respectively, whereas it was 175.49 +/- 9.29 and 173.93 +/- 7.92 in inferior turbinates respectively. The difference between two groups was significant(P < 0.01); (2) The expression of TN and FN in edematous type was significantly stronger than that in cystic fibrous and glandular type (P < 0.05); (3) The association between FN expression and EOS infiltration was significant(r = -0.60, P < 0.01); (4) The expression of TN and FN did not correlate with clinical staging and size(P > 0.05). CONCLUSION Abnormal ECM may contribute to proliferation of epithelium, accumulation of EOS and edema formation, as a result, to enhance the development of nasal polyps.