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中性粒细胞髓过氧化物酶在细菌暴露时产生的氯脂类。

Neutrophil Myeloperoxidase Derived Chlorolipid Production During Bacteria Exposure.

机构信息

Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, United States.

Center for Cardiovascular Research, Saint Louis University School of Medicine, St. Louis, MO, United States.

出版信息

Front Immunol. 2021 Aug 13;12:701227. doi: 10.3389/fimmu.2021.701227. eCollection 2021.

Abstract

Neutrophils are the most abundant white blood cells recruited to the sites of infection and inflammation. During neutrophil activation, myeloperoxidase (MPO) is released and converts hydrogen peroxide to hypochlorous acid (HOCl). HOCl reacts with plasmalogen phospholipids to liberate 2-chlorofatty aldehyde (2-ClFALD), which is metabolized to 2-chlorofatty acid (2-ClFA). 2-ClFA and 2-ClFALD are linked with inflammatory diseases and induce endothelial dysfunction, neutrophil extracellular trap formation (NETosis) and neutrophil chemotaxis. Here we examine the neutrophil-derived chlorolipid production in the presence of pathogenic strain CFT073 and non-pathogenic strain JM109. Neutrophils cocultured with CFT073 strain and JM109 strain resulted in 2-ClFALD production. 2-ClFA was elevated only in CFT073 coculture. NETosis is more prevalent in CFT073 cocultures with neutrophils compared to JM109 cocultures. 2-ClFA and 2-ClFALD were both shown to have significant bactericidal activity, which is more severe in JM109 . 2-ClFALD metabolic capacity was 1000-fold greater in neutrophils compared to either strain of . MPO inhibition reduced chlorolipid production as well as bacterial killing capacity. These findings indicate the chlorolipid profile is different in response to these two different strains of bacteria.

摘要

中性粒细胞是募集到感染和炎症部位的最丰富的白细胞。在中性粒细胞激活过程中,髓过氧化物酶 (MPO) 被释放并将过氧化氢转化为次氯酸 (HOCl)。HOCl 与质膜磷脂反应释放 2-氯脂肪酸醛 (2-ClFALD),其被代谢为 2-氯脂肪酸 (2-ClFA)。2-ClFA 和 2-ClFALD 与炎症性疾病有关,并诱导内皮功能障碍、中性粒细胞胞外陷阱形成 (NETosis) 和中性粒细胞趋化性。在这里,我们研究了在致病性菌株 CFT073 和非致病性菌株 JM109 存在的情况下中性粒细胞衍生的氯脂的产生。与 CFT073 菌株和 JM109 菌株共培养的中性粒细胞导致 2-ClFALD 的产生。仅在 CFT073 共培养物中升高 2-ClFA。与 JM109 共培养物相比,NETosis 在 CFT073 共培养物中的发生更为普遍。2-ClFA 和 2-ClFALD 均表现出显著的杀菌活性,在 JM109 中更为严重。与任何一种菌株相比,中性粒细胞的 2-ClFALD 代谢能力高 1000 倍。MPO 抑制减少了氯脂的产生以及杀菌能力。这些发现表明,对这两种不同的细菌菌株的氯脂谱不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb17/8416994/b847b601857f/fimmu-12-701227-g001.jpg

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