RESUMO
This study analyzed the type 1 and type 2T helper (Th1/Th2) cytokines (including interleukins), immune cellular, matrix profile, and pathogens in granulomas with unexplained etiology compared to those with infectious and noninfectious etiology. Surgical lung biopsies from 108 patients were retrospectively reviewed. Histochemistry, immunohistochemistry, immunofluorescence, morphometry and polymerase chain reaction were used, respectively, to evaluate total collagen and elastin fibers, collagen I and III, immune cells, cytokines, matrix metalloproteinase-9, myofibroblasts, and multiple usual and unusual pathogens. No relevant polymerase chain reaction expression was found in unexplained granulomas. A significant difference was found between the absolute number of eosinophils, macrophages, and lymphocytes within granulomas compared to uninvolved lung tissue. Granulomas with unexplained etiology (UEG) presented increased number of eosinophils and high expression of interleukins (ILs) IL-4/IL-5 and transforming growth factor-ß. In sarcoidosis, CD4/CD8 cell number was significantly higher within and outside granulomas, respectively; the opposite was detected in hypersensitivity pneumonitis. Again, a significant difference was found between the high number of myofibroblasts and matrix metalloproteinase-9 in UEG, hypersensitivity pneumonitis, and sarcoidosis compared to granulomas of tuberculosis. Granulomas of paracoccidioisis exhibited increased type I collagen and elastic fibers. Th1 immune cellular profile was similar among granulomas with unexplained, infectious, and noninfectious etiology. In contrast, modulation of Th2 and matrix remodeling was associated with more fibroelastogenesis and scarring of lung tissue in UEG compared to infectious and noninfectious. We concluded that IL-4/IL-5 and transforming growth factor-ß might be used as surrogate markers of early fibrosis, reducing the need for genotyping, and promise therapeutic target in unexplained granulomas.
Assuntos
Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Pneumopatias/imunologia , Pneumopatias/patologia , Adulto , Matriz Extracelular/patologia , Feminino , Granuloma do Sistema Respiratório/microbiologia , Humanos , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.
Assuntos
Anticorpos Antifúngicos/análise , Hepatopatias/microbiologia , Pneumopatias Fúngicas/microbiologia , Paracoccidioidomicose , Complicações Infecciosas na Gravidez/microbiologia , Animais , Animais Recém-Nascidos , Contagem de Colônia Microbiana , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Granuloma do Sistema Respiratório/microbiologia , Granuloma do Sistema Respiratório/patologia , Hepatopatias/patologia , Pneumopatias Fúngicas/patologia , Tamanho do Órgão , Paracoccidioidomicose/patologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Ratos WistarRESUMO
Tripoli is a microcrystalline siliceous rock used to polish metals and precious stones. Its inhalation has been associated with increased prevalence of breathing complaints and pneumoconiosis. However, its acute human exposure has not been so far studied. We aimed at evaluating the putative mechanical, morphological, biochemical and inflammatory lung damage in mice acutely exposed to Tripoli dust. BALB/c mice were randomly assigned to 2 groups: In control group (CTRL, n=6) animals received intratracheally (i.t.) 0.9% NaCl (50µl), while Tripoli group (TRIP, n=15) received 20mg of Tripoli powder diluted in 50µL of saline i.t. The experiments were done 15 days later. TRIP mice showed higher pulmonary mechanical impedance, polymorphonuclear cells, TNF-α, IL1-ß and IL-6 than CTRL. TRIP presented granulomatous nodules containing collagenous fibers that occupied 35% of the lung tissue area. In conclusion, acute exposure to Tripoli dust triggered important lung damage in mice lungs that if found in human workers could trigger severe illness.
Assuntos
Poeira , Exposição por Inalação/efeitos adversos , Pulmão/patologia , Pulmão/fisiopatologia , Doença Aguda , Animais , Poeira/análise , Feminino , Granuloma do Sistema Respiratório/etiologia , Granuloma do Sistema Respiratório/patologia , Granuloma do Sistema Respiratório/fisiopatologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/etiologia , Pneumonia/patologia , Pneumonia/fisiopatologia , Distribuição Aleatória , Dióxido de Silício/toxicidade , Cloreto de Sódio/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.
Assuntos
Matriz Extracelular/imunologia , Imunidade Celular , Imunofenotipagem/métodos , Sarcoidose/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia , Colágeno/imunologia , Tecido Elástico/imunologia , Tecido Elástico/patologia , Matriz Extracelular/patologia , Feminino , Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Humanos , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Masculino , Pessoa de Meia-Idade , Sarcoidose/patologia , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologiaRESUMO
OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.
OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Matriz Extracelular/imunologia , Imunidade Celular , Imunofenotipagem/métodos , Sarcoidose/imunologia , Análise de Variância , Biópsia , Colágeno/imunologia , Tecido Elástico/imunologia , Tecido Elástico/patologia , Matriz Extracelular/patologia , Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/patologia , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Linfócitos/imunologia , Macrófagos Alveolares/imunologia , Sarcoidose Pulmonar/imunologia , Sarcoidose Pulmonar/patologia , Sarcoidose/patologiaRESUMO
Our medical staff identified a case of a forty-six years old Armed Force active duty female that presented with multiple systemic and pulmonary signs and symptoms, such as hemoptysis, arthralgias, chest pain and dyspnea after being exposed to a humid and old wooden building one year ago in the state of Georgia. Various imaging studies (cervical & thoracic x-rays and CT Scans), revealed diffuse small nodules at cervical & thoracic areas, osteolytic lesions and lymphadenopathy. Suspecting a malignant process, a PET-CT Scan was performed revealing a right lung lower lobe nodule consistent with a primary malignancy, metastatic disease, active infectious or inflammatory process. She underwent a CT-guided needle biopsy followed by an open thoracotomy. These results were negative for malignancy and positive for chronic granulomatous inflammatory process. Therefore, special immunologic stains were undertaken revealing a granulomatous process with Histoplasmosis capsulatum. This case was diagnosed in the most unusual manner, given the presenting symptoms and pathological findings which suggested a malignant process, later confirmed by multiple specialized imaging studies and tests. This presumptive diagnosis turned out to be an inflammatory/infectious (fungal) process. We must keep in mind that not all mass lesions encountered by special imaging studies should be considered malignant. This case exemplifies the need of clinicians to exercise strong clinical and critical thinking skills to consider the broad diagnostic possibilities of pulmonary nodules presenting as a malignancy.
Assuntos
Erros de Diagnóstico , Granuloma do Sistema Respiratório/etiologia , Histoplasmose/diagnóstico por imagem , Pneumopatias Fúngicas/diagnóstico por imagem , Militares , Doenças Profissionais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Nódulo Pulmonar Solitário/etiologia , Tomografia Computadorizada por Raios X , Biópsia por Agulha , Exposição Ambiental , Reações Falso-Positivas , Feminino , Georgia , Granuloma do Sistema Respiratório/diagnóstico por imagem , Granuloma do Sistema Respiratório/patologia , Histoplasma/isolamento & purificação , Histoplasmose/complicações , Histoplasmose/patologia , Humanos , Pneumopatias Fúngicas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Doenças Profissionais/patologia , Osteólise/etiologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Espondilite/etiologia , ToracotomiaRESUMO
Tuberculosis (TB) pleural disease is complicated by extensive tissue destruction. Matrix metalloproteinase (MMP)-1 and -9 are implicated in immunopathology of pulmonary and central nervous system TB. There are few data on MMP activity in TB pleurisy. The present study investigated MMP-1, -2 and -9 and their specific inhibitors (tissue inhibitor of metalloproteinase (TIMP)-1 and -2) in tuberculous effusions, and correlated these with clinical and histopathological features. Clinical data, routine blood tests, and pleural fluid/biopsy material were obtained from 89 patients presenting with pleural effusions in a TB-endemic area. MMP-1, -2 and -9 were measured by zymography or western blot, and TIMP-1 and -2 by ELISA. Pleural biopsies were examined microscopically, cultured for acid-alcohol fast bacilli and immunostained for MMP-9. Tuberculous pleural effusions contained the highest concentrations of MMP-9 compared with malignant effusions or heart failure transudates. MMP-9 concentrations were highest in effusions from patients with granulomatous biopsies: median (interquartile range) 108 (61-218) pg x mL(-1) versus 43 (12-83) pg x mL(-1) in those with nongranulomatous pleural biopsies. MMP-1 and -2 were not upregulated in tuberculous pleural fluid. The ratio of MMP-9:TIMP-1 was significantly higher in TB effusions. Tuberculous pleurisy is characterised by a specific pattern of matrix metalloproteinase-9 upregulation, correlating with the presence of granulomas and suggesting a specific role for matrix metalloproteinase-9 in inflammatory responses in tuberculous pleural disease.
Assuntos
Granuloma do Sistema Respiratório/etiologia , Metaloproteinase 9 da Matriz/metabolismo , Tuberculose Pleural/enzimologia , Tuberculose Pleural/patologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Granuloma do Sistema Respiratório/enzimologia , Granuloma do Sistema Respiratório/patologia , Humanos , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Derrame Pleural/enzimologia , Derrame Pleural/etiologia , Derrame Pleural/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Tuberculose Pleural/complicaçõesRESUMO
Necrotizing sarcoid granulomatosis (NSG) is a rare entity mainly characterized by a prominent granulomatous vasculitis affecting middle-aged or old individuals and with a favorable prognosis. Although many believe it is a variant of sarcoidosis, the proper classification is still a matter of debate as some of its features are found in sarcoidosis but also in Churg-Strauss syndrome, Wegener's disease and hypersensitivity pneumonitis. In this paper, we described for the first time a case of NSG in a family with several cases of sarcoidosis, reinforcing the relationship between NSG and sarcoidosis. Additional interesting findings were the young age of the patient (15 years old), the symptoms limited to the respiratory tract (uncommon when NSG affects youngsters) and the increase in serologic markers of autoimmune disease. Though complete criteria for autoimmune disease were not present, systemic lupus erythematosus and Sjogren's syndrome are possible candidates. As sarcoidosis is described to be associated with several autoimmune diseases, this finding is an additional suggestion of the relationship between both entities.
Assuntos
Granuloma do Sistema Respiratório/genética , Pulmão/patologia , Sarcoidose Pulmonar/genética , Adolescente , Corticosteroides/uso terapêutico , Idoso , Feminino , Granuloma do Sistema Respiratório/tratamento farmacológico , Granuloma do Sistema Respiratório/patologia , Humanos , Pessoa de Meia-Idade , Necrose , Linhagem , Sarcoidose Pulmonar/tratamento farmacológico , Sarcoidose Pulmonar/patologiaRESUMO
Tuberculosis/HIV-1 co-infection is responsible for thousands of deaths each year, and previous studies have reported that co-infected individuals display major morphological alterations in tissue granulomas. The purpose of this study was to evaluate immunohistopathological characteristics in lung tissues from pulmonary TB/HIV-1-co-infected individuals. Following autopsy, tuberculosis-positive HIV-1-negative cases displayed granulomas with normal architecture, mainly composed of a mononuclear infiltrate with typical epithelioid, as well as giant cells, and exhibiting caseous necrosis. In contrast, lesions from the TB/HIV-1-co-infected group showed extensive necrosis, poorly formed granulomas, and a marked presence of polymorphonuclear cells. More importantly, TNF staining was greatly reduced in the TB/HIV-1-co-infected individuals. Our data suggest that HIV-1 infection alters the organization of pulmonary granulomas by modulating TNF and, possibly, cell trafficking, leading to an impaired anti-tuberculosis response.
Assuntos
Granuloma do Sistema Respiratório/imunologia , Infecções por HIV/complicações , Pulmão/imunologia , Tuberculose Pulmonar/complicações , Fator de Necrose Tumoral alfa/biossíntese , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Granuloma do Sistema Respiratório/microbiologia , Granuloma do Sistema Respiratório/patologia , Infecções por HIV/imunologia , Infecções por HIV/patologia , HIV-1 , Humanos , Pulmão/microbiologia , Pulmão/patologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologiaRESUMO
Four patients with clinical diagnosis of interstitial lung disease (ILD) are presented. In these patients, lung biopsies revealed bronchocentric granulomatosis (BG), pulmonary alveolar proteinosis (PAP), diffuse alveolar damage (DAD), and in one biopsy, the clinical manifestations suggested tuberculous primo-infection with systemic dissemination. Three patients died without diagnosis. In all four cases, specific histological stains found Histoplasma capsulatum. Histoplasmosis may mimic other infectious or non-infectious pulmonary diseases, such as interstitial and granulomatous pulmonary disease. Therefore, the absolute need for identification of the organism by culture or special stains cannot be over-emphasized and may lead to a proper mycological diagnosis. This highlights the importance of differential diagnosis with systemic infectious diseases, especially in areas where deep-seated mycosis are endemic.