Activation of RAW264.7 macrophages by oxidized galectin-1.
Galectin-1, a member of the beta-galactoside-binding lectin family, exists in both reduced and oxidized states. Oxidized galectin-1 (Gal-1/Ox), which lacks lectin activity, has been shown to promote axonal regeneration after injury by activating macrophages, which causes the release of factors that enhance Schwann cell migration and neurite outgrowth. However, the mechanism of macrophage activation by Gal-1/Ox remains unknown. In this study, we examined the effects of Gal-1/Ox on RAW264.7 macrophages and RT4-D6P2T Schwann cells. Gal-1/Ox stimulated migration of RT4-D6P2T Schwann cells directly and by activating RAW264.7 macrophages to release factors that promoted cell migration. Gal-1/Ox inhibited nitric oxide (NO) production induced by interferon-gamma by suppressing expression of inducible NO synthase in RAW264.7 macrophages and not by arginase activation and cell death. Furthermore, Gal-1/Ox-activated extracellular signal-regulated protein kinase 1/2 (ERK1/2) in RAW264.7 macrophages, although the mitogen-activated protein kinase (MEK)/ERK1/2 pathway was not involved in release of factors that promoted Schwann cell migration. On the other hand, Gal-1/Ox-induced RT4-D6P2T Schwann cell migration appeared to be mediated by the MEK/ERK1/2 pathway. These results suggest that Gal-1/Ox inhibits inflammatory responses in macrophages and promotes Schwann cell migration directly and by macrophage activation.
Echigo
Yu
Y
Department of Electrical, Engineering and Bioscience, Center for Advanced Biomedical Sciences, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, Japan.
Sugiki
Hayato
H
Koizumi
Yuya
Y
Hikitsuchi
Shinya
S
Inoue
Hiroko
H
D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D017077:Culture Media, Conditioned; D037483:Galectin 1 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects / Q000276:immunology
D017077:Culture Media, Conditioned; D037483:Galectin 1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II