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Lysophosphatidylcholines inhibit human eosinophil activation and suppress eosinophil migration in vivo.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 4.8 ) Pub Date : 2020-03-11 , DOI: 10.1016/j.bbalip.2020.158686
Eva Knuplez 1 , Sanja Curcic 2 , Anna Theiler 1 , Thomas Bärnthaler 1 , Athina Trakaki 1 , Markus Trieb 3 , Michael Holzer 3 , Akos Heinemann 3 , Robert Zimmermann 4 , Eva M Sturm 1 , Gunther Marsche 3
Affiliation  

Eosinophils are important multifaceted effector cells involved in allergic inflammation. Following allergen challenge, eosinophils and other immune cells release secreted phospholipases, generating lysophosphatidylcholines (LPCs). LPCs are potent lipid mediators, and serum levels of LPCs associate with asthma severity, suggesting a regulatory activity of LPCs in asthma development. As of yet, the direct effects of LPCs on eosinophils remain unclear. In the present study, we tested the effects of the major LPC species (16:0, 18:0 and 18:1) on eosinophils isolated from healthy human donors. Addition of saturated LPCs in the presence of albumin rapidly disrupted cholesterol-rich nanodomains on eosinophil cell membranes and suppressed multiple eosinophil effector responses, such as CD11b upregulation, degranulation, chemotaxis, and downstream signaling. Furthermore, we demonstrate in a mouse model of allergic cell recruitment, that LPC treatment markedly reduces immune cell infiltration into the lungs. Our observations suggest a strong modulatory activity of LPCs in the regulation of eosinophilic inflammation in vitro and in vivo.

中文翻译:

溶血磷脂酰胆碱在体内抑制人嗜酸性粒细胞活化并抑制嗜酸性粒细胞迁移。

嗜酸性粒细胞是涉及过敏性炎症的重要的多方面效应细胞。变应原攻击后,嗜酸性粒细胞和其他免疫细胞释放分泌的磷脂酶,产生溶血磷脂酰胆碱(LPC)。LPC是有效的脂质介体,并且LPC的血清水平与哮喘的严重程度相关,表明LPC在哮喘发展中具有调节活性。迄今为止,LPC对嗜酸性粒细胞的直接作用仍不清楚。在本研究中,我们测试了主要LPC种类(16:0、18:0和18:1)对从健康人类供体中分离出来的嗜酸性粒细胞的影响。在存在白蛋白的情况下添加饱和LPC会迅速破坏嗜酸性粒细胞细胞膜上富含胆固醇的纳米域,并抑制多种嗜酸性粒细胞效应子反应,例如CD11b上调,脱粒,趋化性,和下游信令。此外,我们在变态反应性细胞募集的小鼠模型中证明,LPC治疗显着降低了免疫细胞向肺部的浸润。我们的观察结果表明,在体外和体内,LPC在调节嗜酸性粒细胞炎症方面具有很强的调节活性。
更新日期:2020-03-19
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