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Host Defence System (host + defence_system)
Selected AbstractsEffects of edaravone on human neutrophil functionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2005K. Mikawa Background:, Neutrophils play a crucial role in the antibacterial host defence system. Edaravone is used in critically ill patients who are often immuno-compromised secondary to concomitant disease or immunosuppressive therapy. The aim of the current study was to assess the effect of edaravone, a novel free-radical scavenger, on several aspects of human neutrophil function using an in vitro system. Methods:, Chemotaxis, phagocytosis, reactive oxygen species (ROS) production by neutrophil (cellular) and xanthine-xanthine oxidase (acellular) systems, and intracellular calcium ion levels ([Ca2 + ]i) were measured in the absence and in the presence (at a clinically relevant concentration, and 0.1-fold, and 10-fold this concentration) of edaravone. Results:, The clinically relevant concentration of edaravone did not inhibit chemotxais, phagocytosis, or superoxide production of neutrophils. Even at its ordinary clinical plasma concentration, the drug inhibited hydrogen peroxide (H2O2) and hydroxyl radical (OH·) generation in the cellular (neutrophil) as well as in the cell-free (xanthine-xanthine oxidase) system (P < 0.05). Edaravone did not affect elevation of [Ca2 + ]i in neutrophils stimulated by a chemotactic factor. Conclusions:, These findings suggest that edaravone quenched H2O2, and OH· generated rather than impaired the ability of neutrophils to produce the ROS. However, further studies using in vivo systems are required to elucidate the effects of edaravone on neutrophil function in clinical settings. [source] The long-term effects of perinatal glucocorticoid exposure on the host defence system of the respiratory tractTHE JOURNAL OF PATHOLOGY, Issue 1 2006E Theogaraj Abstract Glucocorticoids are used to mature the fetal lung at times of threatened premature delivery. These drugs modify leukocyte profiles when administered in adulthood, but their effects on the mature host defence system following administration during the perinatal period are incompletely understood. In this study, the long-term effects of perinatal dexamethasone exposure on rodent host defence cells in the pulmonary airspaces, the perivascular compartment of the lung, and the blood were investigated. Rats were treated prenatally (gestational days 16,19) or neonatally (postnatal days 1,7) by inclusion of dexamethasone in the mothers' drinking water (1 µg/ml). The pups were then allowed to develop to adulthood (P60-80), at which time respiratory tissues were collected for light and electron microscopy and bronchoalveolar lavage (BAL), and blood for cell count and fluorescent activated cell-sorting (FACS) analysis. Prenatal treatment had no effect on any parameter examined. Following neonatal dexamethasone exposure, light microscopy of the lung tissue revealed a significant reduction in the number of cells in the perivascular space in both the central and the peripheral regions of the adult lung, but no differences in the number of cells in the airspaces. Neonatal dexamethasone exposure was also characterized by a significant reduction in the total number of white cells in the peripheral blood in adulthood and in particular, the number of lymphocytes relative to neutrophils was significantly reduced at maturity in these animals. The results show that neonatal, but not prenatal, dexamethasone exposure significantly alters the distribution of host defence cells in the blood and lung at maturity compared with control animals. The early neonatal period is characterized by the stress hyporesponsive period in the rat, when endogenous glucocorticoid levels are very low. Therefore, exogenous glucocorticoids administered during this time are likely to have marked ,programming' effects on glucocorticoid-sensitive tissues. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Significance of human ,-defensins in the epithelial lining fluid of patients with chronic lower respiratory tract infectionsCLINICAL MICROBIOLOGY AND INFECTION, Issue 1 2007S. Yanagi Abstract Human ,-defensins (hBDs) are the most abundant antimicrobial peptides in epithelial cells, and function in the host immune system. Respiratory epithelial cells express hBDs to inhibit bacterial proliferation during respiratory tract infections. The aim of this study was to investigate the release of hBDs into the respiratory tract and their benefit as a host defence system in chronic Pseudomonas aeruginosa infections. The levels of four hBD peptides (hBD-1,hBD-4) were measured in the bronchial epithelial lining fluid (ELF) of nine patients with chronic lower respiratory tract infection caused by P. aeruginosa. Eight patients with idiopathic pulmonary fibrosis and eight volunteers free of pulmonary disease were recruited as controls. ELF was obtained by bronchoscopic microsampling and hBD levels were measured by radioimmunoassays. The antimicrobial effects of hBDs were studied individually and in combination using an in-vitro colony count assay for P. aeruginosa. Concentrations of hBD-1 and hBD-3 tended to be higher in patients with chronic lower respiratory tract infection than in the controls. hBD-2 and hBD-4 were detected in ELF from five and four of nine patients, respectively, but the hBD levels in controls were all below the limits of detection. All patients with infection caused by mucoid P. aeruginosa had detectable hBD-2 and hBD-4 levels in ELF. In-vitro colony count assays showed a potential synergism between hBD-2 and hBD-4 in inhibiting bacterial proliferation. The findings indicate that hBDs, especially hBD-2 and hBD-4, are pathophysiologically important in infections caused by mucoid strains of P. aeruginosa. [source] | ||||||||||