title: Secretion of endoplasmic reticulum aminopeptidase 1 is involved in the activation of macrophages induced by lipopolysaccharide and interferon-gamma.
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.
authors.affiliation: Laboratory of Cellular Biochemistry, RIKEN, Wako, Saitama, 351-0198, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Goto
authors.forename: Kenji
authors.initials: K
authors.lastname: Ogawa
authors.forename: Akira
authors.initials: A
authors.lastname: Hattori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
mesh_terms: D000626:Aminopeptidases / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D006031:Glycosylation; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008954:Models, Biological; D010587:Phagocytosis
chemical_list: D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D007371:Interferon-gamma; D000626:Aminopeptidases; C509944:ERAP1 protein, mouse