RESUMO
Allergic asthma is the most common phenotype of the pathology, having an early-onset in childhood and producing a Th2-driven airways remodeling process that leads to symptoms and pathophysiological changes. The avoidance of aeroallergen exposure in early life has been shown to prevent asthma, but without repeated success and with the underlying preventive mechanisms at the beginning of asthma far to be fully recognized. In the present study, we aimed to evaluate if neonatal LPS-induced boost in epithelial host defenses contribute to prevent OVA-induced asthma in adult mice. To this, we focused on the response of bronchiolar club cells (CC), which are highly specialized in maintaining the epithelial homeostasis in the lung. In these cells, neonatal LPS administration increased the expression of TLR4 and TNFα, as well as the immunodulatory/antiallergic proteins: club cell secretory protein (CCSP) and surfactant protein D (SP-D). LPS also prevented mucous metaplasia of club cells and reduced the epidermal growth factor receptor (EGFR)-dependent mucin overproduction, with mice displaying normal breathing patterns after OVA challenge. Furthermore, the overexpression of the epithelial Th2-related molecule TSLP was blunted, and normal TSLP and IL-4 levels were found in the bronchoalveolar lavage. A lower eosinophilia was detected in LPS-pretreated mice, along with an increase in phagocytes and regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+), together with higher levels of IL-12 and TNFα. In conclusion, our study demonstrates stable asthma-preventive epithelial effects promoted by neonatal LPS stimulation, leading to the presence of regulatory cells in the lung. These anti-allergic dynamic mechanisms would be overlaid in the epithelium, favored by an adequate epidemiological environment, during the development of asthma.
Assuntos
Asma/imunologia , Bronquíolos/efeitos dos fármacos , Bronquíolos/imunologia , Citocinas/metabolismo , Epitélio/imunologia , Imunidade Inata , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Alérgenos/imunologia , Animais , Animais Recém-Nascidos , Asma/prevenção & controle , Modelos Animais de Doenças , Epitélio/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ovalbumina/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
The Non-Ciliated Bronchiolar Cell (NCBC) is responsible for the defense and maintenance of the bronchiolar epithelium. Several cellular defense mechanisms have been associated with an increase in the secretion of CC16 and changes in the phenotype of the cell; these mechanisms could be linked to tolerance to the damage due to exposure to inhaled Particulate Matter (PM) of the epithelium. These defense mechanisms have not been sufficiently explored. In this article, we studied the response of the NCBC to inhaled vanadium, an element which adheres to PM. This response was measured by the changes in the phenotype of the NCBC and the secretion of CC16 in a mouse model. Mice were exposed in two phases to different vanadium concentrations; 1.27 mg/m³ in the first phase and 2.56 mg/m³ in the second phase. Mice were sacrificed on the 2nd, 4th, 5th, 6th and 8th weeks. In the second phase, we observed the following: sloughing of the NCBC, hyperplasia and small inflammatory foci remained without changes and that the expression of CC16 was higher in this phase than in phase I. We also observed a change in the phenotype with a slow decrease in both phases. The increase in the secretion of CC16 and the phenotype reversion could be due to the anti-inflammatory activity of CC16. The changes observed in the second phase could be attributed to the tolerance to inhaled vanadium.
Assuntos
Bronquíolos , Células Epiteliais , Uteroglobina/metabolismo , Vanádio/toxicidade , Poluentes Atmosféricos/toxicidade , Animais , Anti-Inflamatórios/metabolismo , Bronquíolos/citologia , Bronquíolos/metabolismo , Bronquíolos/patologia , Tolerância a Medicamentos/fisiologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Epitélio/metabolismo , Epitélio/patologia , Inflamação , Inalação , Pulmão/metabolismo , Camundongos , Material Particulado/toxicidadeRESUMO
La publicación describe los criterios para el diagnóstico y tratamiento de bronquiolitis, contribuyendo a la reducción de la morbilidad y mortalidad en menores de 2 años. Asimismo, las medidas de prevención, atención y control de la Bronquiolitis, mejorando así su calidad de vida.
Assuntos
Prevenção Primária , Infecções Respiratórias , Bronquiolite , Guia de Prática Clínica , Assistência Integral à Saúde , BronquíolosRESUMO
Subclinical primary Pneumocystis infection is the most common pulmonary infection in early infancy, making it important to determine whether it damages the lung. Pneumocystis peaks at 2 to 5 months of age, when respiratory morbidity coincidently increases. We have documented that Pneumocystis increases mucus production in infant lungs, and animal models reveal lung lesions that warrant characterization. Herein, immunocompetent rats infected at birth with Pneumocystis by cohabitation, to resemble community-acquired infection, underwent lung assessments at 45, 60, and 75 days of age. Lungs fixed by vascular perfusion to prevent collapse during necropsy were used for morphometry evaluations of mucus production, airway epithelial thickening, perivascular and peribronchiolar inflammation, and structural airway remodeling. Changes in these histologic features indicate lung disease. Selected immune markers were assessed in parallel using fresh-frozen lung tissue from sibling rats of the same cages. Sequential activation of NF-κB and an increased Gata3/T-bet mRNA level ratio, consistent with a type 2 helper T-cell-type inflammatory response, and subacute fibrosis were recognized. Therefore, documenting subclinical Pneumocystis infection induces lung disease in the immunocompetent host. Taken together with the peak age of primary Pneumocystis infection, results warrant investigating the clinical impact of this often subclinical infection on the severity of respiratory diseases in early infancy. This model can also be used to assess the effects of airway insults, including coinfections by recognized respiratory pathogens.
Assuntos
Pneumonia por Pneumocystis/imunologia , Células Th2/imunologia , Animais , Bronquíolos/patologia , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/patologia , Feminino , Regulação da Expressão Gênica/fisiologia , Imunocompetência , Mediadores da Inflamação/metabolismo , Muco/metabolismo , NF-kappa B/metabolismo , Pneumonia por Pneumocystis/patologia , RNA Mensageiro/genética , Ratos Sprague-Dawley , Mucosa Respiratória/patologia , Transdução de Sinais/fisiologiaRESUMO
The massive agricultural expansion converted the Cerdocyon thous, a South American native predator, in vulnerable specie. Basic data, such as histological description, are important to raise awareness on animal species, helping on preservation strategies. Considering the difficult in obtain samples, as the euthanasia of wild animals for this purpose is not allowed, data on histology are very scarce or inexistent. The objective of this paper was to provide a detailed histological description of the trachea and bronchial tree of the crab-eating fox Cerdocyon thous (Linnaeus, 1766). The specimens (one adult male and one adult female) used were provided by the Federal University of Pelotas (Pelotas, RS, Brazil) Rehabilitation Center of Wild Fauna (NURFS). Tissue samples were fixed in 10% formalin and included in paraffin. After slicing, samples were stained with HE (hematoxylin and eosin), PAS (periodic acid-Schiff) and resorcin fuchsin. Trachea had an average diameter of 7.87mm, and approximately 57% of the mucosa ciliated pseudo-stratified columnar epithelium was composed of goblet cells, mostly in the dorsal region. Bronchia and bronchioles had a mucosal fold with higher number of goblet cells. Using all these techniques there is no great remarkable differences from C. thous trachea and lung, when compared with the previous described structures for carnivores and most mammals, except for the goblet cells "regionalization". Described results are important to understand the animal physiological and behavioral habits, allowing the development of preservation and protection strategies.(AU)
A expansão agrícola maciça tornou o Cerdocyon thous, um predador nativo sul-americano, vulnerável. Dados básicos, tais como descrição histológica, são importantes para aumentar o conhecimento sobre as espécies, ajudando nas estratégias de preservação. A eutanásia de animais selvagens para a coleta de amostras não é permitida, por isso os dados sobre a histologia são muito escassos ou inexistentes. O objetivo deste trabalho foi de fornecer uma descrição histológica detalhada da traqueia e árvore brônquica do cachorro do mato Cerdocyon thous (Linnaeus 1766). Os espécimes (um macho e uma fêmea adultos) utilizados foram fornecidos pela Universidade Federal de Pelotas (Pelotas, RS, Brasil), Centro de Reabilitação da Fauna (NURFS). As amostras de tecido foram fixadas em formalina a 10% e incluídas em parafina. Após o corte, as amostras foram coradas com HE (hematoxilina e eosina), PAS (ácido periódico de Schiff) e resorcina fucsina. A traqueia tinha um diâmetro médio de 7,87 milímetros e aproximadamente 57% do diâmetro do epitélio colunar pseudo-estratificado ciliado da mucosa composto por células caliciformes, principalmente na região dorsal do órgão. Os brônquios e bronquíolos apresentaram cararísticas similares aos outros animais, contudo aparenta ter maior número de células caliciformes. Usando distintas técnicas de coloração, observou-se que não há diferenças notáveis da traqueia e do pulmão de C. thous quando comparados com os dados para carnívoros e para a maioria dos mamíferos, exceto a regionalização de células caliciformes. Os resultados descritos são importantes para compreender a fisiologia dos animais e hábitos comportamentais, permitindo o desenvolvimento de estratégias de preservação e proteção.(AU)
Assuntos
Animais , Sistema Respiratório/anatomia & histologia , Traqueia/anatomia & histologia , Canidae/anatomia & histologia , Bronquíolos/anatomia & histologia , Animais Selvagens/anatomia & histologiaRESUMO
The histologic changes occurring in severe/therapy-resistant asthma (SA) as defined by the European Respiratory Society/American Thoracic Society guidelines, particularly at the level of the distal airways are unknown. This study describes the clinical, radiologic, and histologic characteristics of 29 SA patients who underwent video-assisted thoracoscopic surgery lung biopsy. Pathologic observations were correlated with clinical features, especially the presence of autoimmune disease (AID) (15/29, 51.7%). Ten biopsies (10/29, 34.5%) showed only small airway manifestations of asthma, whereas in 19 (65.5%) asthmatic granulomatosis, manifested by asthmatic bronchiolitis supplemented by an alveolar septal mononuclear infiltrates with non-necrotizing granulomas, was present. SA patients without asthmatic granulomatosis showed more striking small airway injury, subbasement membrane thickening, and neutrophilic infiltrates. Cases with concurrent AID had a tendency to more parenchymal eosinophilic inflammation, more bronchiolocentric granulomas, and a suggestion of increased responsivity to nonsteroidal immunosuppressive therapy. Histologic examination of video-assisted thoracoscopic surgery lung biopsies in SA demonstrates diverse pathologies including cases associated with granulomatous inflammation in addition to eosinophilic infiltrates. This spectrum of histologies may link to a high incidence of AID.
Assuntos
Asma/patologia , Doenças Autoimunes/complicações , Bronquíolos/patologia , Granuloma/patologia , Adulto , Asma/complicações , Doenças Autoimunes/epidemiologia , Biópsia , Resistência a Medicamentos , Feminino , Granuloma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Cirurgia Torácica VídeoassistidaRESUMO
PURPOSE: Aging is associated with changes in the lung that leads to a decrease in its function. Alterations in structure and function in the small airways are well recognized in chronic lung diseases. The aim of this study was the assessment of cell turnover in the bronchiolar epithelium of mouse through the normal aging process. METHODS: Lungs from CD1 mice at the age of 2, 6, 12, 18, or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Proliferating cell nuclear antigen was examined by immunohistochemistry. Apoptosis was analyzed by in situ end-labeling of fragmented DNA. Epithelial dimensions were analyzed by morphometry. RESULTS: The 2-month-old mice showed significantly higher number of proliferating cells when compared with mice at all other age groups. The number of apoptotic cells in mice at 24 months of age was significantly greater than in mice at all other age groups. Thus, the number of epithelial cells decreased as the age of the subject increased. We also found reductions in both area and height of the bronchiolar epithelium in mice at 18 and 24 months of age. CONCLUSIONS: We found a decrease in the total number of epithelial cells in the aged mice, which was accompanied by a thinning of the epithelium. These changes reflect a dysregulated tissue regeneration process in the bronchiolar epithelium that might predispose to respiratory diseases in elderly subjects.
Assuntos
Envelhecimento/fisiologia , Bronquíolos/citologia , Bronquíolos/fisiologia , Células Epiteliais/fisiologia , Epitélio/fisiologia , Animais , Apoptose , Proliferação de Células , Senescência Celular , Epitélio/anatomia & histologia , Masculino , Camundongos , Antígeno Nuclear de Célula em Proliferação/metabolismoRESUMO
A novel avipoxvirus caused diphtheritic lesions in the oesophagus of five and in the bronchioli of four Magellanic penguins (Spheniscus magellanicus) and also cutaneous lesions in eight Magellanic penguins housed in outdoor enclosures in a Rehabilitation Centre at Florianópolis, Santa Catarina State, Brazil. At the same time, another avipoxvirus strain caused cutaneous lesions in three Magellanic penguins at a geographically distinct Rehabilitation Centre localized at Vila Velha, Espírito Santo State, Brazil. Diagnosis was based on clinical signs, histopathology and use of the polymerase chain reaction (PCR). Clinical signs in the penguins included cutaneous papules and nodules around eyelids and beaks, depression and restriction in weight gain. The most common gross lesions were severely congested and haemorrhagic lungs, splenomegaly and cardiomegaly. Histological examination revealed Bollinger inclusion bodies in cutaneous lesions, mild to severe bronchopneumonia, moderate periportal lymphocytic hepatitis, splenic lymphopenia and lymphocytolysis. Other frequent findings included necrotizing splenitis, enteritis, oesophagitis, dermatitis and airsacculitis. Cytoplasmic inclusion bodies were seen within oesophageal epithelial cells in five birds and in epithelial cells of the bronchioli in four penguins. DNA from all samples was amplified from skin tissue by PCR using P4b-targeting primers already described in the literature for avipoxvirus. The sequences showed two different virus strains belonging to the genus Avipoxvirus of the Chordopoxvirinae subfamily, one being divergent from the penguinpox and avipoxviruses already described in Magellanic penguins in Patagonia, but segregating within a clade of canarypox-like viruses implicated in diphtheritic and respiratory disease.
Assuntos
Avipoxvirus/genética , Doenças das Aves/epidemiologia , Doenças das Aves/patologia , Doenças das Aves/virologia , Infecções por Poxviridae/veterinária , Spheniscidae , Animais , Oceano Atlântico , Sequência de Bases , Brasil/epidemiologia , Bronquíolos/virologia , Clonagem Molecular , Análise por Conglomerados , Esôfago/virologia , Corpos de Inclusão Viral/patologia , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/veterinária , Infecções por Poxviridae/epidemiologia , Infecções por Poxviridae/patologia , Análise de Sequência de DNA/veterinária , Especificidade da Espécie , Vísceras/patologia , Vísceras/virologiaRESUMO
Bronchiolar Clara cells are integral components of lung homeostasis, predominantly distributed in distal airways. In addition to the 16 kDa Clara cell protein, a major secretory product with anti-inflammatory effects, rat Clara cells express the glycan-binding protein galectin-3 and secrete it into the airways. Given the essential role of galectin-3 in the control of inflammation and the well-established function of glucocorticoids (GCs) in lung physiology, here we investigated whether galectin-3 is a target of the regulatory effects of GCs. Adult male rats were subjected to bilateral adrenalectomy and the lungs were processed for light and transmission electron microscopy, immunoelectron microscopy and Western blot analysis. Profound changes in bronchiolar Clara cells and macrophage morphology could be observed by electron microscopy after adrenalectomy. While specific galectin-3 staining was detected in the nucleus and cytoplasm of Clara cells and macrophages from control animals, cytoplasmic galectin-3 expression was dramatically reduced after adrenalectomy in both cell types. This effect was cell-specific as it did not affect expression of this lectin in ciliated cells. After dexamethasone treatment, galectin-3 expression increased significantly in the nucleus and cytoplasm of macrophages and Clara cells. Western blot analysis showed a clear decrease in galectin-3 expression in ADX animals, which was recovered after a 7-day treatment with dexamethasone. In peritoneal macrophages, galectin-3 expression was also dependent on the effects of GCs both in vivo and in vitro. Our results identify a cell type-specific control of galectin-3 synthesis by GCs in lung bronchiolar Clara cells and interstitial macrophages, which may provide an alternative mechanism by which GCs contribute to modulate the inflammatory response.
Assuntos
Células Epiteliais/metabolismo , Galectina 3/biossíntese , Regulação da Expressão Gênica , Glucocorticoides/farmacologia , Macrófagos/metabolismo , Animais , Western Blotting , Bronquíolos/citologia , Bronquíolos/efeitos dos fármacos , Bronquíolos/metabolismo , Dexametasona/farmacologia , Células Epiteliais/efeitos dos fármacos , Expressão Gênica , Macrófagos/efeitos dos fármacos , Masculino , Microscopia Eletrônica de Transmissão , Microscopia Imunoeletrônica , Ratos , Ratos WistarRESUMO
BACKGROUND: Few studies have addressed small airway (SA) histopathological changes and their possible role in the remodeling process in idiopathic interstitial pneumonias. OBJECTIVES: To study morphological, morphometrical and immunohistochemical features of SA in idiopathic pulmonary fibrosis (usual interstitial pneumonia, UIP) and nonspecific interstitial pneumonia (NSIP). METHODS: We analyzed SA pathology in lung biopsies from 29 patients with UIP and 8 with NSIP. Biopsies were compared with lung tissue from 13 patients with constrictive bronchiolitis (CB) as positive controls and 10 normal autopsied control lungs. We semi-quantitatively analyzed SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-beta, MMP-2, 7, 9, and their tissue inhibitors (TIMP-1, 2). RESULTS: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls. CONCLUSION: We conclude that SAs are pathologically altered and may take part in the lung-remodeling process in idiopathic interstitial pneumonias.
Assuntos
Bronquíolos/patologia , Pneumonias Intersticiais Idiopáticas/patologia , Metaloproteinases da Matriz/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Bronquíolos/metabolismo , Feminino , Humanos , Pneumonias Intersticiais Idiopáticas/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.
Assuntos
Bronquíolos/efeitos dos fármacos , Cocaína Crack/toxicidade , Exposição por Inalação/efeitos adversos , Nariz/efeitos dos fármacos , Sistema Respiratório/efeitos dos fármacos , Administração por Inalação , Azul Alciano/metabolismo , Animais , Corantes/metabolismo , Cocaína Crack/administração & dosagem , Cocaína Crack/sangue , Cocaína Crack/farmacologia , Células Epiteliais/efeitos dos fármacos , Hemossiderina/análise , Imuno-Histoquímica , Macrófagos Alveolares/química , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação do Ácido Periódico de Schiff/métodos , Testes de Toxicidade CrônicaRESUMO
BACKGROUND AND AIMS: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. MATERIALS AND METHODS: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. RESULTS: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r(s) = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV(1))/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. CONCLUSION: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival.