Chandelier
Senior Member (Voting Rights)
Platelet-derived serotonin drives age-related lung pathology in SARS-CoV-2 infection
Marotta et al. report that platelets from middle-aged mice (as well as from aged human healthy donors) release higher levels of serotonin, which promotes platelet aggregation and fibrin deposition in the lungs.
Inhibition of serotonin uptake or blockade of downstream serotonin signaling in a model of COVID-19 ameliorates platelet hyperactivation and protects middle-aged mice from severe disease.
This effect is dependent on fibrin formation but independent of viral replication and immune cell infiltration.
The serotonin-fibrin axis therefore has the potential to serve as a therapeutic target for certain at-risk populations afflicted with COVID-19–related diseases.
—Seth Thomas Scanlon
Here, we show that platelet-released serotonin drives lung pathology in a mouse model of age-associated disease severity after SARS-CoV-2 infection.
In middle-aged mice and aged human healthy donors, platelet serotonin release upon activation was enhanced, and increased morbidity with respiratory dysfunction was associated with activated platelets aggregating and promoting fibrin deposition in the lung microvasculature.
Pharmacologic or genetic disruption of serotonin uptake, or blockade of serotonin-dependent signaling, attenuated platelet activation and protected against respiratory distress, independently of viral replication and immune responses. Inhibition of fibrin formation similarly reduced disease severity, implicating serotonin-driven platelet procoagulant activity as a key contributor to age-related lung dysfunction.
Thus, serotonin-mediated platelet procoagulant activity is a major contributor to respiratory insufficiency during SARS-CoV-2 infection and a potential therapeutic target for preserving pulmonary function, particularly in the elderly.
Web | DOI | Science Immunology | Open Access
Marotta, Davide; Perucchini, Chiara; Grillo, Marta; Fumagalli, Valeria; Di Lucia, Pietro; Rixon, Jordan; Ravà, Micol; Giustini, Leonardo; Malpighi, Chiara; D’Uonnolo, Giulia; Scavone, Mariangela; Mouro, Violette; Abbott, Caitlin; Stachura-Chyla, Natalia; Andreata, Francesco; Scalambrino, Erica; Clerici, Marigrazia; Donnici, Lorena; Longo Minnolo, Marika; Inverso, Donato; De Francesco, Raffaele; Gaya, Mauro; Ruggeri, Zaverio M.; Tripodi, Armando; Podda, Gian Marco; Guidotti, Luca G.; Iannacone, Matteo; De Giovanni, Marco
Editor’s summary
The factors that drive age-related susceptibility to severe COVID-19 and related disorders like COVID-19–associated coagulopathy (CAC) are not completely understood.Marotta et al. report that platelets from middle-aged mice (as well as from aged human healthy donors) release higher levels of serotonin, which promotes platelet aggregation and fibrin deposition in the lungs.
Inhibition of serotonin uptake or blockade of downstream serotonin signaling in a model of COVID-19 ameliorates platelet hyperactivation and protects middle-aged mice from severe disease.
This effect is dependent on fibrin formation but independent of viral replication and immune cell infiltration.
The serotonin-fibrin axis therefore has the potential to serve as a therapeutic target for certain at-risk populations afflicted with COVID-19–related diseases.
—Seth Thomas Scanlon
Abstract
Elderly individuals affected by COVID-19 are vulnerable to severe respiratory failure for reasons that have remained poorly defined.Here, we show that platelet-released serotonin drives lung pathology in a mouse model of age-associated disease severity after SARS-CoV-2 infection.
In middle-aged mice and aged human healthy donors, platelet serotonin release upon activation was enhanced, and increased morbidity with respiratory dysfunction was associated with activated platelets aggregating and promoting fibrin deposition in the lung microvasculature.
Pharmacologic or genetic disruption of serotonin uptake, or blockade of serotonin-dependent signaling, attenuated platelet activation and protected against respiratory distress, independently of viral replication and immune responses. Inhibition of fibrin formation similarly reduced disease severity, implicating serotonin-driven platelet procoagulant activity as a key contributor to age-related lung dysfunction.
Thus, serotonin-mediated platelet procoagulant activity is a major contributor to respiratory insufficiency during SARS-CoV-2 infection and a potential therapeutic target for preserving pulmonary function, particularly in the elderly.
Web | DOI | Science Immunology | Open Access