Platelet-mediated activation of perivascular mast cells triggers progression of sepsis to septic shock in mice
Year: 2025
Type: article
Abstract: The critical events that trigger sepsis progression into life-threatening septic shock remain unclear. In agreement with reports that link a drop in platelet count to a complicated clinical course in sepsis patients, here we report that, during sepsis, mouse platelets become activated, deposit systemically on vascular walls, and stimulate perivascular mast cells (MC) by releasing platelet activating factor (PAF). In mouse models and patient samples, MC activation correlates with the development of shock in sepsis and is mechanistically linked to shock by inducing systemic hypotension, vascular leakage and microvascular perfusion abnormalities. Preventing platelet or MC activation, or inhibiting the activity of the major MC granule constituent chymase, averts progression from sepsis to shock and reduces mortality of septic mice. Thus, our work establishes that, during sepsis progression, platelet microvascular adhesion leads to MC-mediated vascular changes to culminate in septic shock and septic shock-associated mortality. Sepsis may progress into lethal septic shock, but the cellular mechanisms are still unclear. Here the authors show that, in septic mice, platelets activate perivascular mast cells to cause systemic hypotension and vascular pathology, while inhibiting platelets or mast cell activation suppresses septic shock induction, thereby implicating potential therapy targets.
Source: Nature Communications
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, American Heart Association, National Research Foundation, Korea University, National Research Foundation of Korea, National Institutes of Health, Directorate for Engineering, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G1992104789, CAREER: Mapping deep brain functions with super-resolution photoacoustic imaging, G2251352131, G2284106056, G2881237851, Platelet/Mast Cell Interactions as Determinants of End-Organ Injury in Cardiac Surgery, Platelets as regulators of inflammation and tissue injury after cardiac surgery, G3513365402, G3912141637, G4108292983, Platelet- mast cell interactions as determinants of the vascular pathology in septic shock., 3D real-time super-resolution cavitation mapping in laser lithotripsy of urinary stone disease, Head-mounted Photoacoustic Imaging of Deep-brain Neural Activities in Freely Behaving Animals, G5799872395, G6471602708, G666495131, G6671297155, G7041094069, G7359405542, G8126308421, G8455944289, G8798628446, High-resolution High-speed Photoacoustic and Ultrasound Imaging of SmallVessel Functions in Ischemic Stroke, G9000033856, G9000145697, G9000309709
OpenAlex ID: W4416959133