NLRP3 inflammasome activation in platelets in response to sepsis

Autor: Corbin A. Shields, Denise C. Cornelius, Cassandra M. Young, W. Austin Pierce, Cedar H. Baik, Jan M. Williams, Bibek Poudel, Dakota White, Olivia K. Travis
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Lipopolysaccharides
Male
Physiology
Inflammasomes
animal diseases
Interleukin-1beta
030204 cardiovascular system & hematology
Pharmacology
Kidney
sepsis
Rats
Sprague-Dawley
Cecum
0302 clinical medicine
Platelet
Cellular and Molecular Conditions
Disorders and Treatments
Lung
Cells
Cultured
Original Research
Caspase 1
Interleukin-18
Inflammasome
3. Good health
medicine.anatomical_structure
platelets
medicine.symptom
medicine.drug
Blood Platelets
Multiple Organ Failure
Immunology
Inflammation
digestive system
Sepsis
Capillary Permeability
03 medical and health sciences
Immune system
NLRP3
Physiology (medical)
Endothelial permeability
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Platelet activation
Ligation
business.industry
Organ dysfunction
medicine.disease
bacterial infections and mycoses
Platelet Activation
stomatognathic diseases
inflammation
Cellular Physiology
Endothelium
Vascular
business
030217 neurology & neurosurgery
multiorgan injury
Zdroj: Physiological Reports
ISSN: 2051-817X
Popis: Sepsis is a complex syndrome characterized by organ dysfunction and a dysregulated immune host response to infection. There is currently no effective treatment for sepsis, but platelets have been proposed as a potential therapeutic target for the treatment of sepsis. We hypothesized that the NLRP3 inflammasome is activated in platelets during sepsis and may be associated with multiorgan injury in response to polymicrobial sepsis. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in 12‐ to 13‐week‐old male Sprague–Dawley rats. The necrotic cecum was removed at 24 h post‐CLP. At 72 h post‐CLP, activated platelets were significantly increased in CLP versus Sham rats. Colocalization of NLRP3 inflammasome components was observed in platelets from CLP rats at 72 h post‐CLP. Plasma, pulmonary, and renal levels of IL‐1β and IL‐18 were significantly higher in CLP rats compared to Sham controls. Soluble markers of endothelial permeability were increased in CLP versus Sham. Renal and pulmonary histopathology were markedly elevated in CLP rats compared to Sham controls. NLRP3 is activated in platelets in response to CLP and is associated with inflammation, endothelial permeability and multiorgan injury. Our results indicate that activated platelets may play a role to cause multiorgan injury in sepsis and may have therapeutic potential for the treatment of sepsis multiorgan injury.
Databáze: OpenAIRE
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