Secretion of Endoplasmic Reticulum Aminopeptidase 1 Is Involved in the Activation of Macrophages Induced by Lipopolysaccharide and Interferon-γ
Secretion of Endoplasmic Reticulum Aminopeptidase 1 Is Involved in the Activation of Macrophages Induced by Lipopolysaccharide and Interferon-γ
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DOI：
10.1074/jbc.m111.239111
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发表时间：
2011-06-17
影响因子：
4.8
通讯作者：
Tsujimoto, Masafumi
中科院分区：
文献类型：
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作者：
Goto, Yoshikuni;Ogawa, Kenji;Tsujimoto, Masafumi
内质网氨肽酶1（ERAP 1）是一种多功能酶，在加工呈递给内质网I类主要组织相容性复合体的抗原肽中具有重要作用。在这项研究中，我们发现，内质网保留的ERAP 1分泌的巨噬细胞在响应激活处理与脂多糖（LPS）和干扰素（IFN）-γ和增强其吞噬活性。氨肽酶抑制剂amastatin可抑制LPS/IFN-γ诱导的小鼠巨噬细胞RAW264.7吞噬活性的增强。向培养基中添加重组野生型但非失活突变体ERAP 1增强了吞噬作用。这些结果表明，吞噬活性的增强至少部分是由分泌的ERAP 1介导的，通过酶处理的活性肽的产生。我们的数据首次揭示了ERAP 1介导的巨噬细胞活化，并将为这种酶在先天免疫中的作用提供新的见解。
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)-gamma and enhanced their phagocytic activity. Enhancement of the phagocytic activity of murine macrophage RAW264.7 cells induced by LPS/IFN-gamma 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.