Mice Deficient in Angiopoietin-like Protein 2 (Angptl2) Gene Show Increased Susceptibility to Bacterial Infection Due to Attenuated Macrophage Activity.

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 inflammation-associated 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 from Angptl2-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.

• Authors: 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 291 Issue 36 Pg. 18843-52 (09 02 2016) ISSN: 1083-351X [Electronic] United States
• PMID: 27402837 (Publication Type: Journal Article)
• Copyright: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins
• Angptl2 protein, mouse
• Nitric Oxide

Topics

• Angiopoietin-Like Protein 2
• Angiopoietin-like Proteins
• Angiopoietins (genetics, immunology)
• Animals
• Female
• Genetic Predisposition to Disease
• Immunity, Innate
• Macrophages (immunology)
• Mice
• Mice, Knockout
• Nitric Oxide (genetics, immunology)
• Salmonella Infections (genetics, immunology)
• Salmonella typhimurium (immunology)