Protective effect of phosphatidylserine blockade in sepsis induced organ dysfunction

Abstract

BackgroundPhosphatidylserine is usually an intracellularly oriented cell membrane phospholipid. Externalized phosphatidylserine on activated cells is a signal for phagocytosis. In sepsis, persistent phosphatidylserine exposure is also a signal for activation of the coagulation and inflammatory cascades. As such, phosphatidylserine may be a key molecule in sepsis induced cellular and organ injury. We hypothesize that phosphatidylserine blockade provides a protective effect in sepsis induced organ dysfunction. MethodsSepsis was induced in adult female rats using an endotoxin model. Diannexin, a homodimer of annexin A5, was administered for phosphatidylserine blockade. Rats were allocated to control (n = 5), sepsis (n = 6), or sepsis and phosphatidylserine blockade (n = 9) groups. Gut, pulmonary, renal, and hematologic dysfunctions were evaluated by mesenteric microvascular fluid leak, partial pressure of oxygen, serum creatinine, activated clotting time, and glomerular fibrin deposition, respectively. ResultsRats in the sepsis group demonstrated gut, renal, and hematologic dysfunction. Phosphatidylserine blockade reversed signs of gut dysfunction and mesenteric microvascular leak (P < .01). In addition, phosphatidylserine blockade corrected systemic coagulopathy, as measured by activated clotting time (P = .03) and glomerular fibrin deposition (P = .008). There was no difference in renal dysfunction (P = .1) or pulmonary dysfunction in any of the groups (P = .6). ConclusionIn sepsis, phosphatidylserine blockade had a protective effect on gut dysfunction and coagulopathy. Increased phosphatidylserine exposure may be a key mediator of organ dysfunction and coagulopathy during sepsis. These data may provide insights into novel treatment options for septic patients.