RESUMEN
Antrochoanal polyps (ACPs) are an infrequent clinical entity. Cholesterol granulomas (CGs) are commonly associated with chronic middle ear disease but are rare in the paranasal sinuses. We describe a case of a 10-year-old girl with a concomitant CG in an ACP which was surgically excised by nasosinusal endoscopic surgery. To our knowledge, there are only five previously published cases of CGs in ACPs and of these, only two were pediatric cases. We describe a third case in the youngest patient yet reported. Increased intrasinus pressure may affect venous and lymphatic drainage, leading to hemorrhages with hemolysis and deposition of cholesterol crystals and their esters initiating the formation of granulomas in the polyp. In addition, the insufficient lymphatic drainage prevents the complete elimination of lipids, contributing to the formation of cholesterol granulomas. The treatment and the outcome of an ACP associated with a CG are the same as for usual ACPs.
Asunto(s)
Colesterol/análisis , Granuloma/patología , Seno Maxilar/patología , Pólipos Nasales/patología , Enfermedades de los Senos Paranasales/patología , Adenoidectomía , Niño , Diagnóstico Diferencial , Endoscopía , Femenino , Granuloma/diagnóstico por imagen , Granuloma/metabolismo , Granuloma/cirugía , Humanos , Seno Maxilar/diagnóstico por imagen , Seno Maxilar/cirugía , Pólipos Nasales/química , Pólipos Nasales/diagnóstico por imagen , Pólipos Nasales/cirugía , Nasofaringe/patología , Nasofaringe/cirugía , Enfermedades de los Senos Paranasales/diagnóstico por imagen , Enfermedades de los Senos Paranasales/cirugía , Pólipos/química , Pólipos/diagnóstico por imagen , Pólipos/patología , Pólipos/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess counts of α4 and α7 nicotinic acetylcholine receptors in nasal polyps of adults with or without long-term exposure to cigarette tobacco smoke. METHODS: Twenty-two patients with and 22 patients without exposure to cigarette tobacco smoke participated in the study. After endoscopic polypectomy, the fragments of the nasal polyps were analysed by immunohistochemistry. RESULTS: Compared to patients with no exposure, patients with exposure showed higher counts of α4 and α7 nicotinic acetylcholine receptors (t-test, p 0.05). CONCLUSION: Exposure to cigarette tobacco smoke may induce increased counts of α4 and α7 nicotinic acetylcholine receptors in nasal polyps of adults, with lower counts in males than females without exposure to tobacco smoke.
Asunto(s)
Pólipos Nasales/química , Receptores Nicotínicos/análisis , Factores Sexuales , Contaminación por Humo de Tabaco/análisis , Receptor Nicotínico de Acetilcolina alfa 7/análisis , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/patología , Pólipos Nasales/cirugía , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
OBJECTIVE: Motile cilia impairment is a common condition in patients with chronically inflamed airways, such as is seen in nasal polyps (NPs). The mechanism underlying this pathogenic condition is complex and not fully understood. METHODS: We investigated the presence and localization of dynein axonemal heavy chain 5 (DNAH5) in motile cilia using immunofluorescence staining in paraffin-embedded nasal biopsies from NPs (n = 120) and inferior turbinate mucosa (n = 35) of healthy controls. We also performed single-cell staining on cytospin samples (NP = 5, control = 5). Three patterns of DNAH5 localization are defined, including pattern A (presence throughout the axoneme), pattern B (undetectable in the distal part of the axoneme), and pattern C (completely missing throughout the entire axoneme). We developed a semiquantitative scoring system for which 0 = (pattern A > 70%); 1 = (patterns A + B > 70%); and 2 = (pattern C ≥ 30%) in each high-power field (5 fields per sample). RESULTS: Based on our DNAH5 scoring system, the median (1st and 3rd quartile) score was 0.3 (0.2 and 0.4) for samples from controls, and 1.1 (0.6 and 1.6) for samples from NPs in paraffin specimens (P < 0.001). The DNAH5 score had a significant positive relationship with the Lund-Mackay computed tomography score (r = 0.329, P = 0.005) and was higher in patients with eosinophilic NPs (P = 0.006). For cytospin samples, the mean percentage of patterns A, B, and C were 74%, 14%, and 12% in controls, and 48%, 20%, and 32% in NPs, respectively. CONCLUSION: Our results suggest that the absence or mislocalization of DNAH5 from motile cilia is a common and potentially important pathological phenomenon in chronically inflamed airway epithelium. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E97-E104, 2018.
Asunto(s)
Dineínas Axonemales/análisis , Trastornos de la Motilidad Ciliar/metabolismo , Pólipos Nasales/química , Adulto , Biomarcadores/análisis , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/metabolismo , Pólipos Nasales/complicaciones , Cornetes Nasales/metabolismoRESUMEN
Metals have strong toxic effects in humans and can act as immunoregulatory factors. The purpose of our study was to determine whether the concentrations of metals are associated with the clinical course of nasal polyposis (NP). We measured the concentrations of 10 metals and non-metal (Zn, Mn, Se, Fe, Cr, Ni, Pb, Al, Cd, and Cu) in 58 patients with NP, and 29 controls with a healthy nasal mucosa. We used electron microscopy to compare the ultrastructural features of the nasal mucosa between NP patients and healthy controls. Concentrations of metals in nasal polyps and healthy mucosa were determined by mass spectrometry. Transmission electron microscopic (TEM) and scanning electron microscopic (SEM) images of the nasal mucosa were obtained. The mean tissue concentrations of all 10 metals and non-metal were significantly lower in NP patients than in healthy controls (P < 0.05).TEM and SEM revealed changes in the mucosal ultrastructure in NP with progressive fibrosis, devascularisation, and inflammation. Tissue concentrations of metals were lower in NP patients than in healthy controls, and this was particularly evident in massive polyposis.
Asunto(s)
Metales Pesados/análisis , Mucosa Nasal/química , Pólipos Nasales/química , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Italia , Masculino , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Mucosa Nasal/patología , Pólipos Nasales/patologíaRESUMEN
A 39-year-old female presented with a fleshy nasal polyp occluding the left nasal cavity, associated with haemopurulent discharge. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans of the paranasal cavities revealed a large polypoid tumour arising from the left middle turbinate and obstructing the left maxillary sinus ostium. However, no bony or intracranial involvement was identified. A biopsy revealed a tumour with small blue round cell morphology. The tumour cells showed diffuse strong membranous CD99 positivity and patchy CD34 positivity. Ancillary cytogenetic tests for the EWSR1 and SS18/SYT gene translocations were negative. In view of the non-invasive nature of the tumour and the low cell proliferative index (Ki-67) of 5%, a medial maxillectomy resection was performed. The resection revealed additional areas with spindle-cell morphology and focal haemangiopericytic vasculature. The tumour continued to show immunoreactivity to CD99 and CD34, as well as Smooth Muscle Actin (SMA) and Muscle Specific Actin (MSA). The overall findings are in keeping with a sinonasal haemangiopericytoma. With clear surgical resection margins, the patient is on routine follow-up and is currently disease-free.
Asunto(s)
Hemangiopericitoma/patología , Pólipos Nasales/patología , Neoplasias Nasales/patología , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Proliferación Celular , Diagnóstico Diferencial , Femenino , Hemangiopericitoma/química , Hemangiopericitoma/genética , Hemangiopericitoma/cirugía , Humanos , Inmunohistoquímica , Pólipos Nasales/química , Pólipos Nasales/genética , Pólipos Nasales/cirugía , Neoplasias Nasales/química , Neoplasias Nasales/genética , Neoplasias Nasales/cirugía , Valor Predictivo de las PruebasRESUMEN
Sinusitis is a cause of significant morbidity, substantial healthcare costs, and negative effects on quality of life. The primary objective of this study is to characterize the previously unknown lipid profile of sinonasal mucosa from patients with chronic rhinosinusitis (CRS) and from controls. Sinus mucosa samples were analyzed from 9 CRS patients with concomitant nasal polyps, 11 CRS patients without polyps, and 12 controls. Ten lone polyp samples were also analyzed. Samples were subjected to a modified Bligh/Dyer lipid extraction, then high performance thin layer chromatography (HPTLC), combined gas chromatography/electron impact-mass spectrometry (GC/EI-MS), and flow-injection/electrospray ionization-tandem mass spectrometry (FI/ESI-MS/MS). Data was analyzed for identification and profiling of major components. HPTLC revealed an array of species reflecting the lipid complexity of the samples. GC/EI-MS revealed cholesterol and several fatty acids. FI/ESI-MSMS revealed numerous lipid species, namely a host of phosphatidylcholines, phosphatidylethanolamines, ceramides and cholesteryl esters, but no detectable amounts of phosphatidyinositols or sulfated lipids. These results are a first step to uncover unique molecular biomarkers in CRS.
Asunto(s)
Lípidos/química , Pólipos Nasales/química , Sinusitis/fisiopatología , Biomarcadores/química , Estudios de Casos y Controles , Ceramidas/química , Ésteres del Colesterol/química , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Enfermedad Crónica , Humanos , Mucosa Nasal/patología , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Calidad de Vida , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. METHODS AND RESULTS: Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker ß-tubulin in the proximal part of the ciliary axoneme. CONCLUSIONS: We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function.
Asunto(s)
Cilios/enzimología , Óxido Nítrico Sintasa de Tipo I/metabolismo , Mucosa Respiratoria/enzimología , Bronquios/química , Bronquios/enzimología , Células Cultivadas , Cilios/química , Cilios/metabolismo , Humanos , Inmunohistoquímica , Pólipos Nasales/química , Pólipos Nasales/enzimología , Óxido Nítrico Sintasa de Tipo I/química , Mucosa Respiratoria/química , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismoRESUMEN
OBJECTIVE: To investigate endoscopic staging, and nitric oxide levels in the polyp tissue, in patients with nasal polyposis undergoing glucocorticoid therapy. METHODS: Nasal polyposis was evaluated using endoscopic staging and measurement of polyp tissue nitric oxide levels (chemiluminescence method). Forty-five nasal polyposis patients received either nasal therapy (n = 15), oral therapy (n = 15) or combined therapy (n = 15). Pre-treatment and post-treatment staging and nitric oxide levels were evaluated. RESULTS: Endoscopic grading indicated significant post-treatment staging improvements in the oral (p = 0.016) and combined (p = 0.016) groups. Post-treatment staging differed significantly between the three groups (p = 0.041), with greater improvements in the oral and combined groups. All groups showed significantly lower post-treatment nitric oxide levels, compared with baseline, but post-treatment levels did not differ significantly between groups. A significant association was found between treatment response and nitric oxide level alteration. CONCLUSION: This study demonstrates the favourable effects of glucocorticoids on nasal polyposis, and alteration in nitric oxide tissue levels post-treatment. Nitric oxide level in nasal polyp tissue could be an indicator of treatment response, and may aid surgical decision-making by detecting cases that probably will not respond to medical treatment.
Asunto(s)
Glucocorticoides/uso terapéutico , Pólipos Nasales/tratamiento farmacológico , Óxido Nítrico/análisis , Administración Intranasal , Administración Oral , Adulto , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Mucosa Nasal/química , Mucosa Nasal/metabolismo , Pólipos Nasales/química , Pólipos Nasales/metabolismo , Óxido Nítrico/metabolismo , Índice de Severidad de la EnfermedadRESUMEN
Primary small cell carcinoma of the nose and paranasal sinuses is very rare; only a few reports are present in the English literature. The author herein reports a very rare case of primary small cell carcinoma of the maxillary sinus with an emphasis on immunohistochemistry and on KIT and PDGFRA. A 64-year-old man was admitted to our hospital because of left nasal obstruction. Endoscopy revealed three nasal polyps, and imaging modalities revealed an infiltrative tumor (45 x 45 mm) in the left maxillary sinus with invasion into nasal cavity. Multiple biopsies are taken from the nasal lesions. Histologically, the tumor consists of proliferation of malignant small epithelioid cells with hyperchromatic nuclei, fine chromatin, scant cytoplasm, molded nuclei, and absent nucleoli. Immunohistochemically, the malignant cells were positive for cytokeratin (CK) 18, synaptophysin, CD56, p53, Ki-67 (labeling=95%), bcl-2, KIT, and PDGFRA. However, they were negative for pancytokeratins, high molecular weight CK, CK5/6, CK7, CK 14, CK 19, CK20, vimentin, neuron-specific enolase, chromogranin, CD15, CD45, S100 protein, CEA, CA19-9, glial fibrillary acidic protein, neurofilaments, neuroblastoma, CD99, surfactant apoprotein A, melanosome, and TTF-1. The pathologic diagnosis was small cell carcinoma. A molecular genetic analysis using PCR-direct sequencing was performed using paraffin sections, and it showed no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. Imaging modalities including CT, MRI and PET did not reveal any tumors, including the lung, other than the maxillary sinus tumor. The present case is the first of small cell carcinoma of the maxillary sinus with a comprehensive immunohistochemical examination and a gene analysis of KIT and PDGFRA.
Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Pequeñas , Análisis Mutacional de ADN , Inmunohistoquímica , Neoplasias del Seno Maxilar , Pólipos Nasales , Proteínas Proto-Oncogénicas c-kit , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biopsia , Carcinoma de Células Pequeñas/química , Carcinoma de Células Pequeñas/genética , Carcinoma de Células Pequeñas/patología , Proliferación Celular , Endoscopía , Exones , Humanos , Masculino , Neoplasias del Seno Maxilar/química , Neoplasias del Seno Maxilar/genética , Neoplasias del Seno Maxilar/patología , Persona de Mediana Edad , Mutación , Pólipos Nasales/química , Pólipos Nasales/genética , Pólipos Nasales/patología , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-kit/análisis , Proteínas Proto-Oncogénicas c-kit/genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/análisis , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/genética , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. METHODS: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. RESULTS: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. CONCLUSIONS: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.
Asunto(s)
Pólipos Nasales/etiología , Proteínas Adaptadoras de Señalización NOD/fisiología , Sistema Respiratorio/química , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Portadoras/análisis , Proteínas Portadoras/genética , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Inmunidad Innata , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR , Pólipos Nasales/química , Proteínas Adaptadoras de Señalización NOD/análisis , Proteínas Adaptadoras de Señalización NOD/genética , Proteína Adaptadora de Señalización NOD1/análisis , Proteína Adaptadora de Señalización NOD1/genética , Proteína Adaptadora de Señalización NOD2/análisis , Proteína Adaptadora de Señalización NOD2/genética , ARN Mensajero/análisis , Distribución Tisular , Adulto JovenRESUMEN
OBJECTIVE: To acquire basic information concerning the function of the membrane-bound mucin MUC16 in nasal mucosa compared with the best-characterized membrane-bound mucin, MUC4. DESIGN: In vitro study using semiquantatitive reverse transcription-polymerase chain reaction analysis and immunoassay. SETTING: Yeungnam University College of Medicine. SUBJECTS: We examined the nasal polyps obtained during endoscopic sinus surgery in 10 patients, the normal ethmoid sinus mucosa obtained from 10 patients, and human nasal polyp epithelial (HNPE) cells. MAIN OUTCOME MEASURES: Gene expression of MUC4 and MUC16 in nasal polyps and normal nasal mucosa. In addition, we evaluated the effect of 4 physiologically relevant agents, including retinoic acid, interleukin 1beta, phorbol 12-myristate 13-acetate (PMA), and dexamethasone, on the expression of MUC4 and MUC16 in HNPE cells at the gene and protein levels. RESULTS: In nasal polyps, MUC4 was upregulated compared with normal nasal mucosa (P = .009), whereas MUC16 expression did not differ between nasal polyps and normal nasal mucosa. Retinoic acid and interleukin 1beta increased MUC4 expression at the gene and protein level in HNPE cells, whereas MUC16 expression was not affected. Unlike retinoic acid and interleukin 1beta, PMA and dexamethasone increased MUC16 expression, whereas they had no significant effect on MUC4 expression. CONCLUSIONS: Expression of MUC4 and MUC16 are regulated differently in nasal mucosa. Dexamethasone and PMA are potent mediators for the expression of MUC16 in nasal polyps.
Asunto(s)
Antígeno Ca-125/análisis , Proteínas de la Membrana/análisis , Mucina 4/análisis , Mucosa Nasal/química , Adulto , Células Cultivadas , Dexametasona/farmacología , Femenino , Expresión Génica , Humanos , Inmunoensayo , Interleucina-1beta/farmacología , Masculino , Pólipos Nasales/química , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Acetato de Tetradecanoilforbol/farmacología , Tretinoina/farmacologíaRESUMEN
A Surface Plasmon Resonance Imaging (SPRI) sensor has been developed for highly selective determination of cathepsin D (Cat D) or/and E (Cat E). The sensor contains immobilised pepstatin A, which binds aspartyl proteases from solution. Pepstatin A activated with N-Hydroxysuccinimide (NHS) and N-Ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) was immobilized on an amine-modified gold surface. Cysteamine was used for modification of the gold surface. Pepstatin A concentration and pH of interaction were optimised. A concentration of pepstatin equal to 0.5 microg mL(-1) and a pH of 3.75 were selected as optimal. The sensor's dynamic response range is between 0.25 and 1.0 ng mL(-1), and the detection limit is 0.12 ng mL(-1). However, the sensor cannot distinguish between Cat D and Cat E. In order to demonstrate the sensor's potential, Cat E was determined in human red blood cells, Cat D in human saliva, as well as total concentration of Cat D and Cat E in human nasal polyps.
Asunto(s)
Técnicas Biosensibles/métodos , Catepsinas/análisis , Resonancia por Plasmón de Superficie/métodos , Animales , Catepsina D/análisis , Catepsina E/análisis , Eritrocitos/química , Humanos , Pólipos Nasales/química , Pepstatinas/análisis , Saliva/químicaRESUMEN
BACKGROUND: Proteomics has been used as a tool for identification of the protein content of nasal mucus in diseased and healthy subjects. Thirty-five proteins in both chronic rhinosinusitis (CRS) and control groups were identified in a previous study by our group using conventional mass spectrometry analysis. Ten of these proteins were related to innate and acquired immunity and showed differences in expression between the two groups. OBJECTIVE: To investigate the quantitative differential expression of specific nasal mucus proteins previously identified by our group using multiple reaction monitoring (MRM) mass spectrometry in patients with CRS with nasal polyposis compared with normal subjects. METHODS: In a prospective case control study, nasal mucus from patients and control subjects was collected, desalted, resolubilized, and digested using proteolytic enzymes. Previously identified nasal mucus proteins with differential expression in CRS patients were targeted and quantitatively measured using MRM mass spectrometry. RESULTS: Analysis of 12 samples (6 patients and 6 controls) identified 7 of the 10 targeted proteins, many of which were related to innate and acquired immunity. Quantitative analysis showed differential expression in CRS patients compared with control subjects. A detailed analysis and characterization of the protein isolates is outlined. CONCLUSION: This is the first proteomics study of nasal mucus in CRS with polyposis using the MRM technique. The findings suggest that innate and acquired immunity may play a role in the pathophysiology of CRS. Future steps in evaluating the protein characteristics of the mucus of CRS patients are aimed at developing biomarkers and potentially targeted therapies.
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Moco/química , Pólipos Nasales/química , Rinitis/fisiopatología , Sinusitis/fisiopatología , Adulto , Cromatografía Liquida , Enfermedad Crónica , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Inmunidad Innata , Masculino , Espectrometría de Masas/métodos , Persona de Mediana Edad , Pólipos Nasales/inmunología , Proteómica , Rinitis/inmunología , Sinusitis/inmunologíaRESUMEN
This study was designed to investigate the possibility that mtDNA mutations might arise in inflammatory or chronically damaged nasal polyp tissue from 23 patients. Thirteen patients (57%) displayed nasal polyp tissue-specific mtDNA mutations in the hypervariable segment of the control region and cytochrome b gene, which were not found in the corresponding blood cells and/or adjacent normal tissue. Nasal polyp tissue-specific length heteroplasmic mutations were also detected in nucleotide position (np) 303-315 homopolymeric poly C track (39%), np 514-523 CA repeats (17%) and np 16184-16193 poly C track (30%). The average mtDNA copy number was about three times higher in nasal polyp tissue than in the corresponding peripheral blood cells and adjacent non-polyp tissues. The level of reactive oxygen species (ROS) was significantly higher in the nasal polyp tissues compared to those from the corresponding samples. High level of ROS in nasal polyp tissue may contribute to development of mtDNA mutations, which may play a crucial role in the vicious cycle of pathophysiology of nasal polyps.
Asunto(s)
Citocromos b/genética , ADN Mitocondrial/genética , Dosificación de Gen , Mutación , Pólipos Nasales/patología , Adolescente , Adulto , Anciano , Femenino , Histocitoquímica , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/química , Pólipos Nasales/genética , Embarazo , Especies Reactivas de Oxígeno/análisis , Análisis de Secuencia de ADNRESUMEN
Nasal polyps (NP), edematous projections of nasal mucosa (NM), are characterized by an inflammatory cellular infiltrate, however, little is known about etiopathogenesis of NP. Both innate immune mechanisms leading to activation of NF-kappaB and homeostasis of epithelial cells were implicated in the pathogenesis of NP. In this study we investigated the expression of insulin-like growth factor-1 receptor (IGF-1R) and inducible nitric-oxide synthase (iNOS) in NP compared to healthy NM in both the epithelial and stromal compartments. Using immunohistochemistry, frozen tissue sections of NP from 18 patients, and mucosal biopsy specimens of the inferior turbinate from 17 subjects were stained for IGF-1R and iNOS markers. Fluorescence microscopy and computerized image analysis revealed low numbers of IGF-1R-positive cells in all specimens. However, substantially increased numbers of IGF-1R-positive cells were found in NP compared to NM both within the epithelium (1.63 vs. 0.43) and stroma (3.27 vs. 1.03). Positivity for iNOS was detected within the epithelium of NP compared with NM. Numbers of iNOS-positive single cells were highly increased in NP vs. NM in both epithelial (3.83 vs. 1.08) and stromal (4.96 vs. 2.67) compartments. An increased iNOS expression within the epithelial layer as well as increased number of iNOS- and IGF-1R-positive cells in NP was observed. This suggests that innate immune mechanism, and to a lesser extent also growth and homeostasis of epithelial cells, may play a role in formation of NP.
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Células Epiteliales/metabolismo , Pólipos Nasales/química , Óxido Nítrico Sintasa de Tipo II/análisis , Receptor IGF Tipo 1/análisis , Biopsia , Citocinas/metabolismo , Exposición a Riesgos Ambientales , Células Epiteliales/inmunología , Células Epiteliales/patología , Homeostasis , Humanos , Inmunidad Innata , Microscopía Fluorescente , FN-kappa B/metabolismo , Mucosa Nasal/química , Pólipos Nasales/etiología , Pólipos Nasales/inmunología , Método Simple Ciego , Células del Estroma/inmunología , Células del Estroma/metabolismo , Células del Estroma/patologíaRESUMEN
HYPOTHESIS: Neuropeptides released from sensory nerves may contribute to airway inflammation, particularly if their metabolism is impaired through defective inactivation and/or increased production. In the airways, neuropeptides are subjected to degradation by enzymes such as dipeptidyl peptidase (DPP-IV), and are upregulated by neurotrophins such as brain derived neurotrophic factor (BDNF). We therefore assessed in primary human nasal epithelial cells the expression of DPP-IV and BDNF under basal and inflammatory conditions. METHODS: Human epithelial cells were isolated from nasal polyps and middle turbinates, and grown on collagen-coated polycarbonate filters with an air liquid-interface. After three weeks of culture, constitutive cellular expression of DPP-IV and BDNF was assessed by measuring its activity and by ELISA, respectively. To mimick in vivo inflammatory conditions, cells were exposed apically and basolaterally to 50 ng/ml of TNFalpha, IL-1beta, and IFN-gamma for two days. DPP-IV activity and BDNF protein expression were measured in cell lysates and in the apical and basolateral media. RESULTS: Constitutive DPP-IV activity was similar in polyps and turbinates cells. In contrast, polyps epithelial cells expressed higher amounts of BDNF compared to turbinates derived cells. On the other hand, TNFalpha, IL-1beta, and IFN-gamma did not affect DPP-IV activity but significantly increased the cellular expression and the basolateral secretion of BDNF. CONCLUSIONS: Our data show for the first time that primary human airway epithelial cells produced DPP-IV and BDNF under basal conditions. Furthermore, the production and secretion of BDNF were markedly increased in response to pro-inflammatory cytokines, confirming the involvement of BDNF in airway inflammation.
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Factor Neurotrófico Derivado del Encéfalo/biosíntesis , Dipeptidil Peptidasa 4/biosíntesis , Células Epiteliales/metabolismo , Cavidad Nasal/citología , Pólipos Nasales/metabolismo , Factor Neurotrófico Derivado del Encéfalo/análisis , Células Cultivadas , Dipeptidil Peptidasa 4/análisis , Células Epiteliales/química , Humanos , Pólipos Nasales/química , Cornetes NasalesRESUMEN
BACKGROUND: Nasal polyposis (NP) is a chronic inflammatory disease of upper airway with unknown etiology. NP is frequently associated with asthma; the interaction between these comorbidities remains interesting. Oxidative stress has been implicated in the pathophysiology of NP and asthma. The aim of this study is to investigate the significance of oxidative stress in sinonasal microenvironments by evaluating its association with clinopathological parameters and its impacts on the pathogenesis of bronchial hyperresponsiveness (BHR) in NP. METHODS: Polyp biopsy specimens were obtained from 20 nonallergic patients; control mucosas were obtained from 20 volunteers. The levels of free radicals in the tissues and in blood were determined by a sensitive chemiluminescence (CL) method. NP patients were substratified into three subgroups, NP without BHR, NP with asymptomatic BHR, and NP with BHR and asthma by the results of provocative testing. Four histological characteristics of NP, inflammatory cells, eosinophil infiltration, edema and fibrosis were estimated and applied to correlate with the tissue-CL. RESULTS: The mean CL level in polyp-tissues, but not in blood, was higher than in the control specimens. In NP patients, tissue-CL was associated with endoscopy score; high tissue-CL levels were positively correlated with the abundance of inflammatory cells and eosinophils. Tissue-CL and endoscopy score were associated with BHR/asthma phenotype. CONCLUSION: These results suggest an important role for oxidative stress in the pathophysiology of NP and a causal relation between oxidative stress and inflammatory cells, especially the eosinophils. Free radical levels in polyp-tissues associated with NP severity and with BHR/asthma phenotype in nonallergic NP patients.
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Asma/fisiopatología , Hiperreactividad Bronquial/complicaciones , Eosinófilos/patología , Pólipos Nasales/etiología , Estrés Oxidativo , Adulto , Asma/patología , Hiperreactividad Bronquial/patología , Endoscopía , Femenino , Radicales Libres/análisis , Humanos , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Pólipos Nasales/química , Pólipos Nasales/patologíaRESUMEN
BACKGROUND: Staphylococcus aureus-derived enterotoxins (SEs) have been implicated in the pathogenesis of airway inflammatory diseases, especially nasal polyposis. However, the exact role of these molecules in the regulation of eicosanoid synthesis in this pathology remains unexplored. We studied the possible impact of SE-induced immune responses on the eicosanoid production in nasal polyp (NP) patients. METHODS: Tissue sample homogenates from NP patients, with (NP-SEs[+]) and without detectable IgE-antibodies to SEs (NP-SEs[-]; ImmunoCap system), were assayed for IL-5, myeloperoxidase, leukotriene CJD4/E4 (LTC4/D4/E4), LTB4, lipoxin A4, total IgE, and eosinophil cationic protein. RESULTS: Inflammatory makers, eicosanoids, and total IgE were significantly increased in NP-SEs(+) compared with NP-SEs(-) tissues, with the exception of myeloperoxidase, which was similar in both groups. Eicosanoid concentrations correlated to IL-5 and eosinophil cationic protein; however, only cys-leukotriene levels correlated with IgE-antibodies to SEs, independently of allergy and asthma. CONCLUSION: Eicosanoid synthesis is up-regulated in polyp tissue of patients with immune response to SEs and seems to be related to the inflammatory reaction induced by these enterotoxins.
Asunto(s)
Eicosanoides/metabolismo , Enterotoxinas/inmunología , Eosinófilos/inmunología , Pólipos Nasales/inmunología , Rinitis/inmunología , Staphylococcus aureus/inmunología , Adulto , Biomarcadores/análisis , Eicosanoides/análisis , Femenino , Humanos , Inmunoglobulina E/análisis , Interleucina-5/análisis , Masculino , Persona de Mediana Edad , Pólipos Nasales/química , Pólipos Nasales/microbiología , Rinitis/microbiologíaRESUMEN
BACKGROUND: This study analyzes the impact of Staphylococcus aureus enterotoxins (SAEs) and the inflammatory pattern in polyps from China. METHODS: Nasal tissue was obtained from 27 consecutive bilateral nasal polyps and 15 control patients and assayed for eotaxin, interleukin-5, soluble interleukin-2 receptor, transforming growth factor (TGF) beta, myeloperoxidase, eosinophil cationic protein, total IgE, and specific IgE to SAEs. Activated eosinophils were stained using EG2 antibodies in polyps from Chinese and comparative white patients. RESULTS: The number of EG2+ eosinophils was significantly lower in polyps from Chinese patients versus white patients. Chinese polyps showed significantly increased IgE and soluble interleukin-2 receptor versus control samples, whereas TGF-beta1 was significantly decreased. Ten of 27 samples in the polyp group versus 0 of 15 controls contained SAE-IgE (p < 0.01). TGF-beta1 was significantly down-regulated in SAE+ samples versus SAE- samples (p = 0.04). CONCLUSION: Nasal polyps from China are characterized by B- and T-cell activation, a minor eosinophilic inflammation compared with polyps from white subjects, and a decrease in TGF-beta1 in comparison with control inferior turbinate tissue. One-third of patients with polyps showed an IgE response to SAEs.