Galectin-9 protects mice from the Shwartzman reaction by attracting prostaglandin E2-producing polymorphonuclear leukocytes

Clin Immunol. 2007 Aug;124(2):221-33. doi: 10.1016/j.clim.2007.04.015. Epub 2007 Jun 8.


Galectins play a crucial role in the modulation of innate and adaptive immunity. Here we show that galectin-9 (Gal-9) exhibits an anti-inflammatory role in LPS-induced inflammation. Intraperitoneal LPS injection enhances Gal-9 levels as well as promotes the production of pro-inflammatory cytokines, e.g., TNF-alpha, IFN-gamma and IL-12. We found that Gal-9 administration results in the protection of mice from the Shwartzman reaction, and Gal-9-deficient mice became susceptible to the Shwartzman reaction, thus implying the anti-inflammatory activity of Gal-9 against LPS-induced inflammation. Indeed, Gal-9 treatment together with LPS suppresses production of these pro-inflammatory cytokines, while it rather enhances than suppresses IL-4 and IL-10 production. We also found that LPS-induced elevation of TNF-alpha, IFN-gamma, and IL-12 does not occur in Gal-9 transgenic mice. Moreover, Gal-9 induces Gr-1(+) cell; probably polymorphonuclear leukocyte (PMN), as well as infiltration in to the peritoneal cavity, causing us to hypothesize PMNs are involved in Gal-9-mediated suppression. The fact that Gal-9 does not suppress LPS-induced TNF-alpha, IFN-gamma and IL-12 production in neutropenic mice, and that it does not protect those mice from the Shwartzman reaction, confirms the involvement of PMN in regulation. PMN attracted by Gal-9 produce PGE(2), which LPS-induced TNF-alpha production from the peritoneal macrophages is suppressed, while PMNs attracted by casein produce less PGE(2) and fail to suppress LPS-induced TNF-alpha production. Our data suggest that Gal-9 regulates LPS-induced inflammation and protects mice from the Shwartzman reaction by attracting PGE(2)-producing PMN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dinoprostone / biosynthesis
  • Dinoprostone / immunology*
  • Galectins / immunology*
  • Galectins / metabolism
  • Immunity, Innate
  • Interleukin-10 / immunology
  • Lipopolysaccharides / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • Receptors, Prostaglandin E / immunology
  • Receptors, Prostaglandin E, EP4 Subtype
  • Shwartzman Phenomenon / immunology*
  • Th1 Cells / immunology


  • Cytokines
  • Galectins
  • Lipopolysaccharides
  • Ptger4 protein, mouse
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP4 Subtype
  • galectin 9, mouse
  • Interleukin-10
  • Dinoprostone