The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells

Mast cells are thought to contribute significantly to the pathology and mor tality associated with anaphylaxis and other allergic disorders. However, s tudies using genetically mast cell-deficient WBB6F(1)-Kit(W)/Kit(W-v) and c ongenic wild-type (WBB6F(1)(+/+)) mice indicate that mast cells call also p romote health, by participating in natural immune responses to bacterial in fection. We previously reported that repetitive administration of the c-kit ligand, stem cell factor (SCF), can increase mast cell numbers in normal m ice in vivo. In vitro studies have indicated that SCF can also modulate mas t cell effector function.. We now report that treatment with SCF can signif icantly improve the survival of normal C57BL/6 mice in a model of acute bac terial peritonitis, cecal ligation and puncture (CLP). Experiments in mast cell-reconstituted WBB6F1-Kit(W)/Kit(W-v) mice indicate that this effect of SCF treatment reflects, at least in part, the actions of SCF oil mast cell s. Repetitive administration of SCF also carl enhance survival in mice that genetically lack tumor necrosis factor (TNF)-alpha, demonstrating that the ability of SCF treatment to improve survival after CLP does not solely ref lect effects of SCF on mast cell-dependent (or -independent) production of TNF-alpha, These findings identify c-kit and mast cells as potential therap eutic targets for enhancing innate immune responses.