RESUMO
BACKGROUND: Matrix metalloproteinases (MMPs) are responsible for the breakdown of the extracellular matrix and play an important role in the inflammatory processes of pleural exudates. The imbalance between MMPs and their inhibitors (TIMPs) is present in various pathological processes. OBJECTIVE: To evaluate the profile of MMPs and TIMPs in pleural effusions of different etiologies correlated with inflammatory markers. METHODS: The patients with pleural effusion due to tuberculosis (TB), cancer (CA) or transudate were prospectively evaluated. Pleural fluid was submitted to cytological, biochemical, cytokines, MMP, and TIMP analysis. Statistical analysis was performed using ANOVA and Spearman's correlation, and p < 0.05 was considered significant. RESULTS: One hundred and fourteen patients were enrolled, 80 exudates (41 TB and 39 CA) and 34 transudates. The levels of MMP-8 and MMP-9 were higher in exudates compared to transudates. The level of MMP-8 was significantly higher in TB than in CA. TIMP-1 levels were higher in exudates. IL-6, VEGF, and TGF-ß1 showed differences between exudates and transudates. However, IL-6 level was higher in TB than in CA. We found a significant correlation between MMPs and TIMPs with inflammation markers. MMP-1 was correlated with LDH levels. MMP-8 was correlated with LDH, total cell count, neutrophils, and ADA as well as MMP-1 levels. MMP-9 was correlated with IL-6, TGF-ß1, and VEGF. TIMP-1 was correlated with MMP-9 and IL-6. CONCLUSIONS: MMPs and TIMPs are expressed in pleural fluid of different etiologies and correlate with inflammatory mediators. MMPs may be useful in determining the cause of fluid, but more studies are needed to determine the spectrum of diseases associated with the various isoforms of MMPS and TIMPs.
Assuntos
Exsudatos e Transudatos/enzimologia , Metaloproteases/metabolismo , Derrame Pleural Maligno/enzimologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Tuberculose Pulmonar/enzimologia , Adenosina Desaminase/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Exsudatos e Transudatos/metabolismo , Feminino , Humanos , Inflamação , Interleucina-6/metabolismo , L-Lactato Desidrogenase/metabolismo , Contagem de Leucócitos , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 8 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Neutrófilos , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/metabolismo , Derrame Pleural Maligno/patologia , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto JovemRESUMO
In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.
Assuntos
Angiostrongylus/imunologia , Dinoprostona/fisiologia , Edema/terapia , Eosinofilia/enzimologia , Ácidos Hidroxieicosatetraenoicos/fisiologia , Hipersensibilidade/terapia , Isoenzimas/metabolismo , Lipoxinas , Prostaglandina-Endoperóxido Sintases/metabolismo , Infecções por Strongylida/enzimologia , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Antígenos de Helmintos/administração & dosagem , Corticosterona/sangue , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/administração & dosagem , Dinoprostona/metabolismo , Edema/enzimologia , Edema/patologia , Edema/fisiopatologia , Eosinofilia/patologia , Eosinofilia/fisiopatologia , Exsudatos e Transudatos/efeitos dos fármacos , Exsudatos e Transudatos/enzimologia , Feminino , Ácidos Hidroxieicosatetraenoicos/metabolismo , Hipersensibilidade/enzimologia , Hipersensibilidade/patologia , Hipersensibilidade/fisiopatologia , Injeções Intraperitoneais , Injeções Intravenosas , Interleucina-5/administração & dosagem , Isoenzimas/farmacologia , Cinética , Leucotrieno C4/metabolismo , Masculino , Misoprostol/administração & dosagem , Derrame Pleural/enzimologia , Derrame Pleural/metabolismo , Derrame Pleural/patologia , Derrame Pleural/prevenção & controle , Pleurisia/enzimologia , Pleurisia/patologia , Pleurisia/fisiopatologia , Prostaglandina-Endoperóxido Sintases/farmacologia , Ratos , Ratos Wistar , Infecções por Strongylida/patologia , Infecções por Strongylida/fisiopatologiaRESUMO
Blister formation and skin damage can be induced by BaP1, a haemorrhagic metalloproteinase from the venom of the snake Bothrops asper. Pathological changes in the skin were investigated after intramuscular injections of Bothrops asper haemorrhagic metalloproteinase BaP1. Blisters developed within the first hour, with separation of epidermis from the dermal-epidermal junction, whereas acantholysis of epithelial cells was not observed. After the third hour there was ulceration with formation of a proteinaceous scab and inflammatory infiltrate. By 7 to 14 days there was evidence of a regenerative process in dermis and epidermis. Haemorrhage occurred in both dermis and hypodermis as a consequence of BaP1 injection, together with damage of sebaceous glands and an inflammatory reaction in which enlarged macrophages were the predominant cell type. Zymography assays showed the presence of several endogenous metalloproteinases in the exudate, skin homogenates and plasma. In addition, BaP1 was detected in exudates and plasma by immunoblotting. This technique also demonstrated the presence of components immunologically related to laminin and collagen type IV in exudates. It is suggested that BaP1, and probably endogenous matrix metalloproteinases, degrade some protein components at the dermal-epidermal junction, inducing the formation of blisters.
Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Metaloendopeptidases/toxicidade , Dermatopatias/induzido quimicamente , Animais , Vesícula/induzido quimicamente , Vesícula/enzimologia , Vesícula/patologia , Eletroforese em Gel de Poliacrilamida , Proteínas da Matriz Extracelular/metabolismo , Exsudatos e Transudatos/enzimologia , Exsudatos e Transudatos/metabolismo , Gelatinases/metabolismo , Immunoblotting , Metaloendopeptidases/metabolismo , Camundongos , Dermatopatias/enzimologia , Dermatopatias/patologiaRESUMO
The activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied. According to the etiology of exudative pleural effusions, the patients were divided into the following five groups: (1) tuberculosis; (2) lung cancer; (3) pneumonias; (4) miscellaneous; and (5) idiopathic. Patients with pleural tuberculosis presented significantly higher ADA activity than patients with nontuberculous pleural effusions (p less than 0.0001). The results indicated that in a population with a relatively high prevalence of tuberculosis, the analysis of ADA levels in pleural effusions constitutes a useful marker for the diagnosis which, in addition, can be made quickly and cheaply. Additionally, a comprehensive review of the literature on the role of ADA in the diagnosis of tuberculous pleural effusions is presented.