Purinergic signaling and immune responses in sepsis #MMPMID27156007
Ledderose C; Bao Y; Kondo Y; Fakhari M; Slubowski C; Zhang J; Junger WG
Clin Ther 2016[May]; 38 (5): 1054-65 PMID27156007show ga
Purpose: Sepsis remains an unresolved clinical problem with high hospital mortality. Despite intensive research over decades, no treatments for sepsis have become available. Here we explore the role of adenosine triphosphate (ATP) in the pathophysiology of sepsis. ATP is not only a universal energy carrier but it also acts as an extracellular signaling molecule that regulates immune functions. ATP stimulates a large family of purinergic receptors found on the cell surface of virtually all mammalian cells. In severe sepsis and septic shock, ATP released in large amounts into the extracellular space acts as a ?danger signal?. In this review, we focus on the roles of ATP as a key regulator of immune cell function and as a disruptive signal that contributes to immune dysfunction in sepsis. Methods: We summarized the current understanding of the pathophysiology of sepsis with special emphasis on the emerging role of systemic ATP as a disruptive force that promotes morbidity and mortality in sepsis. Findings: Over the last two decades, the discovery that regulated ATP release and purinergic signaling represent a novel regulatory mechanism in immune cell physiology has opened up new possibilities to treat sepsis. Immune cells respond to stimulation with the release of cellular ATP, which regulates cell functions in autocrine and paracrine fashions. In sepsis, large amounts of systemic ATP produced by tissue damage and inflammation disrupt these regulatory purinergic signaling mechanisms, leading to immune dysfunction that promotes pathophysiological processes involved in sepsis. Implications: The knowledge of these ATP-dependent signaling processes is likely to reveal exciting new avenues to treat the unresolved clinical problem of sepsis.
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Clin+Ther 2016 ; 38 (5): 1054-65
