Adrenoreceptors are involved in the stimulation of neutrophils by exercise-induced circulating concentrations of Hsp72: cAMP as a potential "intracellular danger signal"

Abstract

Recently, the terms "stress mediators" or "danger signals" have come to be used to describe endogenous molecules that can be released in stress situations and activate the innate immune system even in the absence of antigenic stimuli. There is evidence suggesting that extracellular heat shock proteins of 72 kDa (eHsp72), together with noradrenaline (NA), are candidates as danger signals during exercise-induced stress, interacting in the activation of neutrophils. Previous studies have shown that the post-exercise circulating concentration of eHsp72 activates the phagocytic process of neutrophils with the participation of toll-like receptor 2, but that other receptors must also be involved. The present investigation evaluates the role of adrenoreceptors in the activation of the chemotaxis, phagocytosis, and fungicidal capacity of neutrophils by the post-exercise circulating concentration of eHsp72. The results showed that intact α- and β-adrenoreceptors are necessary for the stimulation of all stages of the phagocytic process by eHsp72. Also, eHsp72 increased the intracellular levels of cAMP, suggesting that it is an "intracellular danger signal" during stress-induced activation of neutrophils mediated by extracellular heat shock proteins. These results can contribute to better understanding the mechanisms involved in the regulation of the innate immune response mediated by "danger signals" during exercise, and probably during other stress situations.