Fibrinogen Like Protein 2 (FGL2): A Novel Regulator of Macrophage M1 Polarization

Fibrinogen-like protein 2 (FGL2) is a potent immunosuppressive molecule. The effects of FGL2 on macrophages, however, has not been studied. Peritoneal cell accumulation in fgl2-/-, fgl2+/+ and fgl2Tg mice in response to thioglycollate was measured. Significantly fewer cells were recovered from the peritoneal cavity of fgl2Tg mice compared to fgl2+/+ or fgl2-/- mice after thioglycollate injection. The difference in cell numbers was found to be due to decreased eosinophil accumulation in fgl2Tg mice. The effect of FGL2 on macrophage M1 and M2 polarization was next examined. IL-12 was significantly reduced in macrophages isolated from fgl2Tg mice. Addition of recombinant FGL2 protein to fgl2+/+ macrophages led to suppression of IL-12 production in a dose-dependent manner. Finally, Flow cytometric analysis of fgl2Tg macrophages revealed reduced expression of TLR4 as well as decreased phagocytosis. These data demonstrate that FGL2 inhibits the proinflammatory activity of macrophages and provides a rationale for developing anti-FGL2 therapies.M.Sc