Law Hannah L, Wright Rachael D, Iqbal Asif J, Norling Lucy V, Cooper Dianne
The William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Front Pharmacol. 2020 Mar 20;11:274. doi: 10.3389/fphar.2020.00274. eCollection 2020.
Galectin-1 (Gal-1) exerts immune-regulatory and anti-inflammatory actions in animal models of acute and chronic inflammation. Its release into the extracellular milieu often correlates with the peak of inflammation suggesting that it may serve a pro-resolving function. Gal-1 is reported to inhibit neutrophil recruitment and induce surface exposure of phosphatidylserine (PS), an "eat me" signal on the surface of neutrophils, yet its role in resolution remains to be fully elucidated. We hypothesized that the anti-inflammatory and pro-resolving properties of Gal-1 are mediated through its ability to inhibit neutrophil recruitment and potentiate neutrophil clearance. To investigate this, a murine model of self-resolving inflammation was utilized to uncover the role of both the endogenous and exogenous protein using Gal-1 null mice and recombinant protein, respectively. We found that peritoneal macrophages express increased Gal-1 during the resolution phase and enhanced neutrophil recruitment occurs in the early phases of zymosan peritonitis in Gal-1 null mice compared to their wild-type (WT) counterparts. Administration of recombinant Gal-1 following the peak of inflammation led to reduced neutrophil numbers at 24 and 48 h, shortening the resolution interval from 39 to 14 h. Gal-1 treatment also enhanced neutrophil apoptosis, indicating a pro-resolving action. Together these results indicate an important role for Gal-1 in the timely resolution of acute inflammation.
半乳糖凝集素-1（Gal-1）在急慢性炎症动物模型中发挥免疫调节和抗炎作用。它释放到细胞外环境中常常与炎症高峰相关，这表明它可能具有促进炎症消退的功能。据报道，Gal-1可抑制中性粒细胞的募集并诱导中性粒细胞表面磷脂酰丝氨酸（PS）的暴露，PS是中性粒细胞表面的一种“吃我”信号，但其在炎症消退中的作用仍有待充分阐明。我们推测，Gal-1的抗炎和促进炎症消退特性是通过其抑制中性粒细胞募集和增强中性粒细胞清除的能力介导的。为了研究这一点，我们分别利用Gal-1基因敲除小鼠和重组蛋白，采用自我消退炎症的小鼠模型来揭示内源性和外源性蛋白的作用。我们发现，在炎症消退阶段，腹膜巨噬细胞表达的Gal-1增加，与野生型（WT）小鼠相比，Gal-1基因敲除小鼠在酵母聚糖性腹膜炎早期中性粒细胞募集增强。在炎症高峰后给予重组Gal-1导致24小时和48小时时中性粒细胞数量减少，将消退时间间隔从39小时缩短至14小时。Gal-1治疗还增强了中性粒细胞凋亡，表明其具有促进炎症消退的作用。这些结果共同表明Gal-1在急性炎症的及时消退中起重要作用。
