关键词:
Macrophages
Cumene hydroperoxide
alpha-Tocopherol
Phagocytic functions
Mannose receptors
摘要:
Macrophages, the major phagocytes of body, are largely dependent on membrane for their apposite functioning. Cum-OOH, a catalyst used in chemical and pharmaceutical industry, is a peroxidative agent, which may induce oxidative stress in macrophages hampering the integrity of their membrane. alpha-Tocopherol is known to protect the membrane from oxidative modulation and preserve its integrity. In the present study, we investigated the effect of Cum-OOH on physiology of macrophages and evaluated the protective effect of a-tocopherol against Cum-OOH-induced functional impairment. An in vitro exposure to 10-200 mu M Cum-OOH altered redox balance of murine peritoneal macrophages and led to a severe physiological impairment. It markedly augmented the release of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta and prostaglandin E-2), lipopolysaccharide primed nitric oxide release and inducible nitric oxide synthase expression, and lysosomal hydrolases secretion. It mitigated respiratory burst and phagocytosis and intracellular killing of yeast (Saccharomyces cereviseae). Mannose receptor, a major macrophage phagocytic receptor (also implicated in S. cereviseae phagocytosis), exhibited a hampered recycling with its number being reduced to about 54% of the untreated, control cells following Cum-OOH exposure. A 24-h pretreatment of macrophages with 25 mu M alpha-tocopherol preserved most of the assessed functions close to their corresponding control values. These data suggest that exposure to Cum-OOH may impair the physiology of immune cells such as macrophages and that supplementation with alpha-tocopherol can safeguard these cells against Cum-OOH toxicity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.