Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Am J Pathol. 2013 May;182(5):1681-95. doi: 10.1016/j.ajpath.2013.01.042. Epub 2013 Mar 15.
Scavenger receptor A5 (SCARA5) is a member of the class A scavenger receptors, with most similarity to SCARA1 (SR-A) and SCARA2 (MARCO), which are primarily expressed by macrophages and dendritic cells, in which they participate in clearance of various polyanionic macromolecules, pollution particles, and pathogens. The biological role of SCARA5 has been unknown. Herein, we show that SCARA5 is an endocytotic receptor whose ligand repertoire includes the typical scavenger receptor ligands, whole bacteria, and purified Gram-negative bacterial lipopolysaccharide. In contrast to expression of SCARA1 and SCARA2 in immune cells, SCARA5 is found in a subset of fibroblast-like cells in the interstitial stroma of most organs, with additional expression in the epithelial cells of testis and choroid plexus. SCARA5-null mice develop with age lymphoid cell accumulation in many organs, in particular the lungs, and show decreased endocytotic function in fibroblasts. Furthermore, about one-third of the mice develop antinuclear antibodies. These disturbances are reminiscent of those found in many human autoimmune connective tissue disorders, which suggests that defects in fibroblast SCARA5 can underlie some forms of autoimmune disease.
清道夫受体 A5（SCARA5）是 A 类清道夫受体家族的成员，与巨噬细胞和树突状细胞中主要表达的 SCARA1（SR-A）和 SCARA2（MARCO）最为相似，它们参与清除各种多阴离子大分子、污染颗粒和病原体。SCARA5 的生物学作用尚不清楚。本文中，我们发现 SCARA5 是一种内吞受体，其配体谱包括典型的清道夫受体配体、完整细菌和纯化的革兰氏阴性细菌脂多糖。与 SCARA1 和 SCARA2 在免疫细胞中的表达不同，SCARA5 存在于大多数器官间质基质中的一组成纤维细胞样细胞中，在睾丸和脉络丛的上皮细胞中也有表达。SCARA5 基因敲除小鼠随年龄增长会在许多器官中积累淋巴细胞，尤其是肺部，并且成纤维细胞的内吞功能下降。此外，约三分之一的小鼠产生抗核抗体。这些紊乱类似于许多人类自身免疫性结缔组织疾病中发现的紊乱，这表明成纤维细胞 SCARA5 的缺陷可能是某些自身免疫性疾病的基础。
