Scrutinizing Mechanisms of the 'Obesity Paradox in Sepsis': Obesity Is Accompanied by Diminished Formation of Neutrophil Extracellular Traps (NETs) Due to Restricted Neutrophil-Platelet Interactions

Systemic inflammation is a detrimental condition associated with high mortality. However, obese individuals seem to have higher chances of surviving sepsis. To elucidate what immunological differences exist between obese and lean individuals we studied the course of endotoxemia in mice fed high-fat...

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Published in:Cells (Basel, Switzerland) Switzerland), 2021-02, Vol.10 (2), p.384
Main Authors: Cichon, Iwona, Ortmann, Weronika, Santocki, Michal, Opydo-Chanek, Malgorzata, Kolaczkowska, Elzbieta
Format: Article
Language:English
Subjects:
Animals
Blood Platelets - drug effects
Diet, High-Fat - adverse effects
Disease Models, Animal
endotoxemia
Extracellular Traps - drug effects
Extracellular Traps - immunology
Inflammation - drug therapy
Inflammation - immunology
Inflammation - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Obese
neutrophil extracellular traps
Neutrophil Infiltration - drug effects
neutrophils
Neutrophils - drug effects
Neutrophils - immunology
Obesity - drug therapy
Obesity - immunology
platelets
sepsis
systemic inflammation
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Summary:Systemic inflammation is a detrimental condition associated with high mortality. However, obese individuals seem to have higher chances of surviving sepsis. To elucidate what immunological differences exist between obese and lean individuals we studied the course of endotoxemia in mice fed high-fat diet (HFD) and ob/ob animals. Intravital microscopy revealed that neutrophil extracellular trap (NET) formation in liver vasculature is negligible in obese mice in sharp contrast to their lean counterparts (ND). Unlike in lean individuals, neutrophil influx is not driven by leptin or interleukin 33 (IL-33), nor occurs via a chemokine receptor CXCR2. In obese mice less platelets interact with neutrophils forming less aggregates. Platelets transfer from ND to HFD mice partially restores NET formation, and even further so upon P-selectin blockage on them. The study reveals that in obesity the overexaggerated inflammation and NET formation are limited during sepsis due to dysfunctional platelets suggesting their targeting as a therapeutic tool in systemic inflammation.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10020384