RESUMEN
Efferocytosis is believed to be a key regulator for lung inflammation in chronic obstructive pulmonary disease. In this study we pharmacologically inhibited efferocytosis with annexin V and attempted to determine its impact on the progression of pulmonary emphysema in mouse. We first demonstrated in vitro and in vivo efferocytosis experiments using annexin V, an inhibitor for phosphatidylserine-mediated efferocytosis. We then inhibited efferocytosis in porcine pancreatic elastase (PPE)-treated mice. PPE-treated mice were instilled annexin V intranasally starting from day 8 until day 20. Mean linear intercept (Lm) was measured, and cell apoptosis was assessed in lung specimen obtained on day 21. Cell profile, apoptosis, and mRNA expression of matrix metalloproteinases (MMPs) and growth factors were evaluated in bronchoalveolar lavage (BAL) cells on day 15. Annexin V attenuated macrophage efferocytosis both in vitro and in vivo. PPE-treated mice had a significant higher Lm, and annexin V further increased that by 32%. More number of macrophages was found in BAL fluid in this group. Interestingly, cell apoptosis was not increased by annexin V treatment both in lung specimens and BAL fluid, but macrophages from mice treated with both PPE and annexin V expressed higher MMP-2 mRNA levels and had a trend for higher MMP-12 mRNA expression. mRNA expression of keratinocyte growth factor tended to be downregulated. We showed that inhibited efferocytosis with annexin V worsened elastase-induced pulmonary emphysema in mice, which was, at least partly, attributed to a lack of phenotypic change in macrophages toward anti-inflammatory one.
Asunto(s)
Anexina A5/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos Alveolares/enzimología , Elastasa Pancreática/efectos adversos , Enfisema Pulmonar/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Lavado Broncoalveolar , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Macrófagos Alveolares/patología , Metaloproteinasa 12 de la Matriz/biosíntesis , Metaloproteinasa 2 de la Matriz/biosíntesis , Ratones , Elastasa Pancreática/farmacología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/enzimología , Enfisema Pulmonar/patología , ARN Mensajero/biosíntesis , PorcinosRESUMEN
Spirometry is practically the only tool to evaluate pulmonary functions. Other automatic systems comparable to spirometry are expected. A fiber-grating (FG) vision sensor is a non-contact respiratory monitoring system to detect changes in volumes by measuring the movement of laser spots on the body surface. We examined the contributions of the FG sensor to evaluating pulmonary functions. The FG sensor showed a linear correlation with spirometry in tidal volumes (TV) obtained from five controls (R = 0.98, P < 0.0001). We also showed agreement of TV between the two devices using Bland-Altman analysis. TV measured by the FG sensor were reproducible and applicable to distinct subjects. To detect airway obstruction, we performed forced expiration in controls (n = 16) and chronic obstructive pulmonary disease (COPD) patients (n = 18) with the FG sensor and spirometry. Forced expiratory volume in 1 s (FEV(1)) and FEV(1)/forced vital capacity in COPD patients were lower than those in controls by the FG sensor. In addition, prolonged expiration in natural breathing by the FG sensor was related to airflow limitation by spirometry. The FG sensor was helpful to measure volume changes and to evaluate pulmonary functions in controls and patients with COPD. Its upcoming clinical applications are promising for simplicity and feasibility.
Asunto(s)
Vidrio/química , Salud , Fenómenos Ópticos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/instrumentación , Pruebas de Función Respiratoria/métodos , Adulto , Estudios de Casos y Controles , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Respiración , Espirometría , Volumen de Ventilación Pulmonar/fisiología , Factores de TiempoRESUMEN
In order to investigate influences of discharge rates on fluvial transport behavior of elements in the Kuji River, Japan, suspended and dissolved phase concentrations in the river water were measured together with the water flow rates. The concentrations of suspended particulate matter (SPM) increased by two or three orders of magnitude with the water discharge, and also had seasonal variations. Adsorptive elements or heavy metal elements, which tend to form insoluble compounds, were present generally as suspended forms in the river waters, and their dissolved form concentrations tended to increase with the water discharge. On the other hand, non-adsorptive elements such as alkali and alkaline-earth elements were present as dissolved forms under a normal flow rate condition, but equivalent quantity of suspended species also occurred under a high flow condition. In this case, the dissolved form concentrations decreased with the water discharge. Characterization of SPM with analyses of chemical compositions, scanning electron microscopy (SEM) and X-ray diffractometry (XRD) indicated that clay mineral such as montmorillonite would be the main carrier material of trace and major elements during the fluvial transport in the Kuji River. Variations of contents of selected elements in SPM with the water discharge indicated that river bottom sediments, which are probably potential sources of SPM added due to high water flow rates, would be different in chemical compositions from SPM floating under a normal flow condition. Variations of chemical compositions of SPM as well as of suspended or dissolved form concentrations of elements in the river waters were formulated as a function of the water discharge rates.