Temperature can prime human peripheral blood neutrophils in a p38MAPKalpha-dependent manner.

INTRODUCTION Previous ex vivo experiments by others suggest that elevated body temperature can prime the respiratory burst of human neutrophils. The mechanism of the priming phenomenon induced by temperature has not been addressed so far. Furthermore, the priming temperature range was not defined. MATERIAL/METHODS In the present study we explored ,under in vitro conditions, the influence of febrile-range temperatures on reactive oxygen species (ROS)generation by human peripheral blood neutrophils. ROS production was measured using whole.blood luminol-dependent chemiluminescence. Two elements of signal transduction pathways, calcium and p38 mitogen.activated protein kinase alpha (p38MAPKalpha) ,frequently underlying neutrophil priming were also examined. Calcium levels in the cytosol of resting and fMLP. stimulated isolated neutrophils were measured with the Fura-2AM spectrofluorimetric method. The activity of p38MAPKalpha was assessed indirectly with a specific inhibitor of the kinase, SB 203580. RESULTS The study revealed a priming effect at 38 degrees C toward human peripheral blood neutrophil ROS production. Any concomitant effect on calcium response was not observed. Instead, experiments with SB 203580,a specific inhibitor of p38MAPKalpha, pointed to an increased activity of the kinase as a molecular background of temperature-induced priming. However, the priming effect of temperature was confined to 38 degrees C, while higher temperatures proved to exert no effect (39 and 40 degrees C)or even inhibited ROS generation by neutrophils (43 degrees C). CONCLUSIONS Our study suggests a heterogeneous influence of temperature on human neutrophil functioning, including the priming of the cells by a low-febrile-range temperature. It also suggests a p38MAPKalpha-dependent molecular background of the priming phenomenon.