内质网氨肽酶 1 的分泌参与脂多糖和干扰素-γ诱导的巨噬细胞活化。
Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma.
机构信息
Laboratory of Cellular Biochemistry, RIKEN, Wako, Saitama, 351-0198, Japan.
出版信息
J Biol Chem. 2011 Jun 17;286(24):21906-14. doi: 10.1074/jbc.M111.239111. Epub 2011 Apr 29.
Abstract
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme with an important role in processing antigenic peptides presented to class I major histocompatibility complex in the endoplasmic reticulum. In this study, we found that endoplasmic reticulum-retained ERAP1 was secreted from macrophages in response to activation by treatment with lipopolysaccharide (LPS) and interferon (IFN)-γ and enhanced their phagocytic activity. Enhancement of the phagocytic activity of murine macrophage RAW264.7 cells induced by LPS/IFN-γ was inhibited by a potent aminopeptidase inhibitor, amastatin. The addition of recombinant wild-type but not inactive mutant ERAP1 to culture medium enhanced phagocytosis. These results suggest that enhancement of phagocytic activity is at least in part mediated by secreted ERAP1 through the generation of active peptides processed by the enzyme. Our data reveal ERAP1-mediated activation of macrophages for the first time and will provide new insights into the role of this enzyme in innate immunity.
摘要
内质网氨肽酶 1（ERAP1）是一种多功能酶，在抗原肽呈递给内质网中 I 类主要组织相容性复合物方面具有重要作用。在这项研究中，我们发现，内质网中保留的 ERAP1 可被脂多糖（LPS）和干扰素（IFN）-γ激活的巨噬细胞分泌，并增强其吞噬活性。用强效氨肽酶抑制剂 amastatin 抑制 LPS/IFN-γ诱导的小鼠巨噬细胞 RAW264.7 细胞吞噬活性的增强。向培养基中添加重组野生型而非无活性突变体 ERAP1 可增强吞噬作用。这些结果表明，吞噬活性的增强至少部分是通过酶处理产生的活性肽介导的分泌型 ERAP1 来实现的。我们的数据首次揭示了 ERAP1 介导的巨噬细胞激活，这将为该酶在先天免疫中的作用提供新的见解。
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