Department of Pathology The Second Affiliated Hospital School of Medicine Xi'an Jiaotong University, Xi'an 710004, China.
Core Research Laboratory The Second Affiliated Hospital School of Medicine Xi'an Jiaotong University, Xi'an 710004, China.
J Immunol Res. 2024 Jul 10;2024:2899154. doi: 10.1155/2024/2899154. eCollection 2024.
As another receptor for complement activation product C5a, C5aR2 has been paid much attention these years. Although controversial and complex, its specific signals or roles in modulating the classic receptor C5aR1 have been investigated and gradually revealed. The hypothesis of the heterodimer of C5aR1 and C5aR2 has also been suggested and observed under extremely high C5a concentrations. In this article, we tried to investigate whether C5aR2 would affect C5aR1 expression under normal or inflammatory conditions in WT and mice of C57BL/6 background. We focused on the innate immune cells-neutrophils and macrophages. The mRNA levels of in normal kidney, liver, and the mRNA or protein levels of naïve-bone marrow and peripheral blood leukocytes and peritoneal Ms were comparable between WT and mice, indicating the technique of C5aR2 knockout did not affect the transcription of its neighboring gene C5aR1. However, the mean fluorescence intensity of surface C5aR1 on naïve circulating neutrophils detected by FACS was reduced, which might be due to the reduced internalization of C5aR1 on neutrophils. In the peritonitis model induced by . injection of thioglycollate, more neutrophils were raised after 10 hr in peritoneal cavity, indicating the antagonism of C5aR2 on C5aR1 signal in neutrophil chemotaxis. After 3 days of thioglycollate injection, the mainly infiltrating macrophages were comparable between WT and mice, but the mRNA and surface or total C5aR1 protein expression were both reduced in macrophages, combined with our previous study of reduced chemokines and cytokines expression in peritoneal macrophages, indicating that C5aR2 in macrophages may cooperate with C5aR1 inflammatory signals. Our article found C5aR2 deficiency lessened C5aR1 distribution and expression in neutrophils and macrophages with different functions, indicating C5aR2 might function differently in different cells.
作为补体激活产物 C5a 的另一个受体，C5aR2 近年来受到了广泛关注。尽管存在争议且复杂，但已经研究并逐渐揭示了其在调节经典受体 C5aR1 方面的特定信号或作用。在极高的 C5a 浓度下，C5aR1 和 C5aR2 的异二聚体假说也被提出并观察到。在本文中，我们试图研究在 WT 和 C57BL/6 背景下的 小鼠中，正常或炎症条件下 C5aR2 是否会影响 C5aR1 的表达。我们重点关注先天免疫细胞-中性粒细胞和巨噬细胞。在正常肾脏、肝脏中，WT 和 小鼠的 基因的 mRNA 水平相当，幼稚骨髓和外周血白细胞以及腹膜 Ms 的 mRNA 或蛋白水平也相当，这表明 C5aR2 敲除技术不影响其相邻基因 C5aR1 的转录。然而，通过 FACS 检测到的幼稚循环 中性粒细胞表面 C5aR1 的平均荧光强度降低，这可能是由于 中性粒细胞上 C5aR1 的内化减少所致。在用. 注射硫代乙醇酸盐诱导腹膜炎模型中，10 小时后 腹腔中的中性粒细胞增多，表明 C5aR2 对中性粒细胞趋化作用中 C5aR1 信号的拮抗作用。硫代乙醇酸盐注射 3 天后，WT 和 小鼠腹膜中的主要浸润巨噬细胞相当，但 巨噬细胞中的 mRNA 和表面或总 C5aR1 蛋白表达均降低，结合我们之前关于腹腔巨噬细胞中趋化因子和细胞因子表达减少的研究，表明巨噬细胞中的 C5aR2 可能与 C5aR1 炎症信号协同作用。我们的文章发现 C5aR2 缺乏减少了具有不同功能的中性粒细胞和巨噬细胞中 C5aR1 的分布和表达，表明 C5aR2 在不同细胞中可能发挥不同的作用。
