Mice deficient in angiopoietin-like protein 2 (ANGPTL2) gene show increased susceptibility to bacterial infection due to attenuated macrophage activity

Masaki Yugami, Haruki Odagiri, Motoyoshi Endo, Hiroyasu Tsutsuki, Shigemoto Fujii, Tsuyoshi Kadomatsu, Tetsuro Masuda, Keishi Miyata, Kazutoyo Terada, Hironori Tanoue, Hitoshi Ito, Jun Morinaga, Haruki Horiguchi, Taichi Sugizaki, Takaaki Akaike, Tomomi Gotoh, Toshiyuki Takai, Tomohiro Sawa, Hiroshi Mizuta, Yuichi Oike

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6 Citations (Scopus)

Abstract

Macrophages play crucial roles in combatting infectious disease by promoting inflammation and phagocytosis. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor that induces tissue inflammation by attracting and activating macrophages to produce inflammatory cytokines in chronic inflammationassociated diseases such as obesity-associated metabolic syndrome, atherosclerosis, and rheumatoid arthritis. Here, we asked whether and how ANGPTL2 activates macrophages in the innate immune response. ANGPTL2 was predominantly expressed in proinflammatory mouse bone marrow-derived differentiated macrophages (GM-BMMs) following GM-CSF treatment relative to anti-inflammatory cells (M-BMMs) established by M-CSF treatment. Expression of the proinflammatory markers IL-1β, IL-12p35, and IL-12p40 significantly decreased in GM-BMMs fromAngptl2-deficient compared with wild-type (WT) mice, suggestive of attenuated proinflammatory activity. We also report that ANGPTL2 inflammatory signaling is transduced through integrin α5β1 rather than through paired immunoglobulin-like receptor B. Interestingly, Angptl2-deficient mice were more susceptible to infection with Salmonella enterica serovar Typhimurium than were WT mice. Moreover, nitric oxide (NO) production by Angptl2-deficient GM-BMMs was significantly lower than in WT GM-BMMs. Collectively, our findings suggest that macrophage-derived ANGPTL2 promotes an innate immune response in those cells by enhancing proinflammatory activity and NO production required to fight infection.

Original languageEnglish
Pages (from-to)18843-18852
Number of pages10
JournalJournal of Biological Chemistry
Volume291
Issue number36
DOIs
Publication statusPublished - 2016 Sep 2

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yugami, M., Odagiri, H., Endo, M., Tsutsuki, H., Fujii, S., Kadomatsu, T., Masuda, T., Miyata, K., Terada, K., Tanoue, H., Ito, H., Morinaga, J., Horiguchi, H., Sugizaki, T., Akaike, T., Gotoh, T., Takai, T., Sawa, T., Mizuta, H., & Oike, Y. (2016). Mice deficient in angiopoietin-like protein 2 (ANGPTL2) gene show increased susceptibility to bacterial infection due to attenuated macrophage activity. Journal of Biological Chemistry, 291(36), 18843-18852. https://doi.org/10.1074/jbc.M116.720870