Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment Part A: Early acute phase of sepsis: an extraordinary redox situation (leukocyte-endothelium interaction leading to endothelial damage)

Xavier Forceville (1, 2, 3) , Pierre van Antwerpen (4) , Jean-Charles Preiser (5)

1 CIC - Centre d'Investigation Clinique [Rennes]
2 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
3 Centre Hospitalier de Meaux
4 ULB - Université libre de Bruxelles
5 ULB - Hôpital Erasme [Bruxelles]

SIGNIFICANCE: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. CRITICAL ISSUES: Neutrophil production increases dramatically and aggressive, immature forms are released. Leukocyte cross-talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia-reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the endothelial surface layer, reducing flow and damaging the endothelial barrier. Future Direction: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step towards organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.

Mots clés: endothelium; free radicals; leukocyte activation; oxidative stress; redox state; selenium

Domaines: Sciences du Vivant [q-bio]

Xavier Forceville, Pierre van Antwerpen, Jean-Charles Preiser. Selenocompounds and sepsis: redox bypass hypothesis for early diagnosis and treatment Part A: Early acute phase of sepsis: an extraordinary redox situation (leukocyte-endothelium interaction leading to endothelial damage). Antioxidants and Redox Signaling, 2021, 35 (2), pp.113-138. ⟨10.1089/ars.2020.8063⟩. ⟨hal-03156442⟩