The parenchymal microglia possess different morphological characteristics in cerebral physiological and pathological conditions; thus, visualizing these cells is useful as a means of further investigating parenchymal microglial function. Annexin A3 (ANXA3) is expressed in microglia, but it is unknown whether it can be used as a marker protein for microglia and its physiological function. Here, we compared the distribution and morphology of parenchymal microglia labeled by ANXA3, cluster of differentiation 11b (CD11b), and ionized calcium-binding adaptor molecule 1 (Iba1) and measured the expression of ANXA3 in nonparenchymal macrophages (meningeal and perivascular macrophages). We also investigated the spatiotemporal expression of ANXA3, CD11b, and Iba1 in vivo and in vitro and the cellular function of ANXA3 in microglia. We demonstrated that ANXA3-positive cells were abundant and evenly distributed throughout the whole brain tissue and spinal cord of adult rats. The morphology and distribution of ANXA3-labeled microglia were quite similar to those labeled by the microglial-specific markers CD11b and Iba1 in the central nervous system (CNS). ANXA3 was expressed in the cytoplasm of microglia, and its expression was significantly increased in activated microglia. ANXA3 was almost undetectable in the nonparenchymal macrophages. Meanwhile, the protein and mRNA expression levels of ANXA3 in different regions of the CNS were different from those of CD11b and Iba1. Moreover, knockdown of ANXA3 inhibited the proliferation and migration of microglia, while overexpression of ANXA3 enhanced these activities. This study confirms that ANXA3 may be a novel marker for parenchymal microglia in the CNS of adult rats and enriches our understanding of ANXA3 from expression patterns to physiological function.

中文翻译：

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膜联蛋白 A3 作为大鼠中枢神经系统小胶质细胞的标记蛋白

实质小胶质细胞在脑生理病理条件下具有不同的形态特征；因此，可视化这些细胞可用作进一步研究实质小胶质细胞功能的一种手段。膜联蛋白A3（ANXA3）在小胶质细胞中表达，但能否作为小胶质细胞的标志蛋白及其生理功能尚不清楚。在这里，我们比较了由 ANXA3、分化簇 11b (CD11b) 和离子化钙结合衔接分子 1 (Iba1) 标记的实质小胶质细胞的分布和形态，并测量了 ANXA3 在非实质巨噬细胞（脑膜和血管周围巨噬细胞）中的表达。我们还研究了 ANXA3、CD11b 和 Iba1 在体内和体外的时空表达以及 ANXA3 在小胶质细胞中的细胞功能。我们证明了ANXA3阳性细胞丰富且均匀分布在成年大鼠的整个脑组织和脊髓中。ANXA3 标记的小胶质细胞的形态和分布与中枢神经系统 (CNS) 中小胶质细胞特异性标志物 CD11b 和 Iba1 标记的非常相似。ANXA3在小胶质细胞的细胞质中表达，在活化的小胶质细胞中其表达显着增加。ANXA3 在非实质巨噬细胞中几乎检测不到。同时，ANXA3在中枢神经系统不同区域的蛋白和mRNA表达水平与CD11b和Iba1不同。此外，ANXA3 的敲低抑制了小胶质细胞的增殖和迁移，而 ANXA3 的过表达增强了这些活性。