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Platelet HMGB1 is required for efficient bacterial clearance in intra-abdominal bacterial sepsis in mice
- Publication Year :
- 2018
- Publisher :
- American Society of Hematology, 2018.
-
Abstract
- Thrombocytopenia impairs host defense and hemostasis in sepsis. However, the mechanisms of how platelets regulate host defense are not fully understood. High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis. Platelets express HMGB1, which is released on activation and has been shown to play a critical role in thrombosis, monocyte recruitment, and neutrophil extracellular trap (NET) production. However, the contribution of platelet HMGB1 to host defense is unknown. To determine the role of platelet HMGB1 in polymicrobial sepsis, platelet-specific HMGB1 knockout (HMGB1 platelet factor 4 [PF4]) mice were generated and were subjected to cecal ligation and puncture (CLP), a clinically relevant intra-abdominal sepsis model. Compared with HMGB1 Flox mice and wild-type (WT) mice, HMGB1 PF4 mice showed significantly higher bacterial loads in the peritoneum and blood, an exaggerated systemic inflammation response, and significantly greater mortality after CLP. Deletion of HMGB1 in platelets was associated with lower platelet-derived chemokines (PF4 and RANTES) in the peritoneal cavity, and a decrease of platelet-neutrophil interaction in the lung after CLP. In vitro, neutrophils cocultured with activated HMGB1 knockout platelets showed fewer platelet-neutrophil aggregates, reduced reactive oxygen species (ROS) burst as compared with control. Taken together, these data reveal an unrecognized role of platelet HMGB1 in the regulation of neutrophil recruitment and activation via modulation of platelet activation during sepsis.
- Subjects :
- 0301 basic medicine
Blood Platelets
Male
Neutrophils
chemical and pharmacologic phenomena
Mice, Transgenic
Cell Communication
HMGB1
Extracellular Traps
Neutrophil Activation
Sepsis
03 medical and health sciences
Peritoneal cavity
Mice
medicine
Animals
Platelet
Platelet activation
HMGB1 Protein
biology
business.industry
Abdominal Cavity
Hematology
Neutrophil extracellular traps
medicine.disease
Platelets and Thrombopoiesis
Platelet Activation
Adoptive Transfer
Bacterial Load
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Hemostasis
Immunology
biology.protein
business
Reactive Oxygen Species
Platelet factor 4
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....40649051d1cff4792fd15808f80acccf