Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages

• Published in: Scientific reports Vol. 6; no. 1; p. 35014
• Main Authors: Toyonaga, Takahiko, Matsuura, Minoru, Mori, Kiyoshi, Honzawa, Yusuke, Minami, Naoki, Yamada, Satoshi, Kobayashi, Taku, Hibi, Toshifumi, Nakase, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.10.2016; Nature Publishing Group
• Subjects: 13/106; 38/77; 631/250/2504/342; 64/60; 692/4020/1503/257; 82/80; Animals; Colitis - genetics; Colitis - microbiology; Colon; Disease Models, Animal; E coli; Escherichia coli - physiology; Gene Knockout Techniques; Humanities and Social Sciences; Humans; Immunology; Inflammation; Inflammatory bowel disease; Interleukin-10 - genetics; Lipocalin-2 - genetics; Lipocalin-2 - metabolism; Macrophages; Macrophages - immunology; Macrophages - microbiology; Mice; Mice, Knockout; multidisciplinary; Neutrophils; Phagocytosis; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep35014

Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice. Lcn2 expression in the colonic tissues of IL-10 KO mice increased with the development of colitis. Lcn2/IL-10 double-KO mice showed a more rapid onset and development of colitis compared to IL-10 KO mice. Lcn2 enhanced phagocytic bacterial clearance in macrophages in vitro after infection with Escherichia coli . Transfer of Lcn2-repleted macrophages prevented the development of colitis in Lcn2/IL-10 double-KO mice in vivo . Our findings revealed that Lcn2 prevents the development of intestinal inflammation. One crucial factor seems to be the enhancement of phagocytic bacterial clearance in macrophages by Lcn2.