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Abstract-Neutrophils are completely differentiated cells that die in tissues a few days after they migrate from the vascular compartment as a consequence of a rigouous apoptotic program. Many of the mediators produced during an inflammatory response delay neutrophil apoptosis allowing a more efficient removal of microorganisms but also favoring the tissue damage by reactive oxygen species (ROS) and lysosomal proteins released by neutrophils. Glucocorticoids delay the apoptosis of neutrophils but the mechanisms are not completely understood. To investigate the inhibition of glucocorticoids on neutrophil apoptosis we have used the glucose/glucose oxidase (G /GO) system as a constant source of hydrogen peroxide. When neutrophils are incubated in the presence of the G /GO system, a significant acceleration of their apoptotic response is observed. Preincubation with 10-6 M, 10-7 M, 10-8 M or 10-9 M of dexamethasone, negatively modulated the spontaneous and G /GO induced apoptosis of neutrophils. Then the G /GO system is a useful model to simulate the oxidative stress of neutrophils, and that the effect of DXM on neutrophil apoptosis depends, at least in part, on blocking the proapoptotic effect of ROS.
KEY WORDS: Neutrophils; apoptosis; reactive oxygen species; dexamethasone
INTRODUCTION
Polymorphonuclear neutrophils (PMN) play a pivotal role in the host defense against microorganisms and in the physiopathology of the inflammatory response. They are produced in human bone marrow at a rate of over 0.85 x 109 cells per kilogram per day. After circulating in the blood for about 6-8 hr they move to the tissues, but if they do not migrate to the tissues or are not recruited to sites of inflammation, they undergo pro-grammed cell death and are usually phagocytosed by resident macrophages in the liver or spleen. The neutrophils live for only a few days in the tissues, though an individual cell may survive for a long a 2 weeks (1).
The antimicrobial activity of neutrophils is due to the capacity to produce reactive oxygen species (ROS). Production of these reactive oxygen species depends on the activation of an enzymatic system known as NADPH oxidase, which tranfers electrons from cytosolic NADPH to phagolysosomal O2 to produce superoxide anion (O2) and starting from O2 different toxic products are formed (2, 3). Activation of the NADPH oxidase leads to an increase of...