锡克
炎症
趋化因子
免疫学
促炎细胞因子
人口
脾脏
生物
体内
细胞生物学
医学
酪氨酸激酶
信号转导
环境卫生
生物技术
作者
Kurt Bachmaier,Andrew Stuart,Abhalaxmi Singh,Asok Mukhopadhyay,Sreeparna Chakraborty,Zhigang Hong,Li Wang,Yoshikazu Tsukasaki,Mark Maienschein‐Cline,Balaji Ganesh,Prasad Kanteti,Jalees Rehman,Asrar B. Malik
出处
期刊:ACS Nano
[American Chemical Society]
日期:2022-03-01
卷期号:16 (3): 4084-4101
被引量:16
标识
DOI:10.1021/acsnano.1c09762
摘要
The complex involvement of neutrophils in inflammatory diseases makes them intriguing but challenging targets for therapeutic intervention. Here, we tested the hypothesis that varying endocytosis capacities would delineate functionally distinct neutrophil subpopulations that could be specifically targeted for therapeutic purposes. By using uniformly sized (∼120 nm in diameter) albumin nanoparticles (ANP) to characterize mouse neutrophils in vivo, we found two subsets of neutrophils, one that readily endocytosed ANP (ANPhigh neutrophils) and another that failed to endocytose ANP (ANPlow population). These ANPhigh and ANPlow subsets existed side by side simultaneously in bone marrow, peripheral blood, spleen, and lungs, both under basal conditions and after inflammatory challenge. Human peripheral blood neutrophils showed a similar duality. ANPhigh and ANPlow neutrophils had distinct cell surface marker expression and transcriptomic profiles, both in naive mice and in mice after endotoxemic challenge. ANPhigh and ANPlow neutrophils were functionally distinct in their capacities to kill bacteria and to produce inflammatory mediators. ANPhigh neutrophils produced inordinate amounts of reactive oxygen species and inflammatory chemokines and cytokines. Targeting this subset with ANP loaded with the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, mitigated the effects of polymicrobial sepsis by reducing tissue inflammation while fully preserving neutrophilic host-defense function.
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