Department of Experimental Hematology, Institute of Zoology and Biomedical Research, Jagiellonian University, 30-387 Krakow, Poland.
Cells. 2021 Feb 12;10(2):384. doi: 10.3390/cells10020384.
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.
全身炎症是一种有害的状态，与高死亡率相关。然而，肥胖个体似乎有更高的存活脓毒症的机会。为了阐明肥胖和瘦个体之间存在什么免疫差异，我们研究了高脂饮食（HFD）喂养的小鼠和 ob/ob 动物的内毒素血症的过程。活体显微镜检查显示，肥胖小鼠肝脏血管中中性粒细胞胞外陷阱（NET）的形成可忽略不计，与瘦小鼠形成鲜明对比（ND）。与瘦个体不同，中性粒细胞的涌入不是由瘦素或白细胞介素 33（IL-33）驱动的，也不是通过趋化因子受体 CXCR2 发生的。在肥胖小鼠中，与中性粒细胞相互作用的血小板较少，形成的聚集体较少。血小板从 ND 转移到 HFD 小鼠中部分恢复了 NET 的形成，而在它们上阻断 P-选择素后则进一步恢复。该研究表明，在肥胖症中，由于血小板功能障碍，脓毒症期间过度的炎症和 NET 形成受到限制，这表明它们作为全身炎症的治疗工具具有靶向性。
