C1q promotes recognition and engulfment of H. pylori infected AGS cells and modulates inflammatory cytokine production in macrophages. (P4019)

Abstract

Abstract H pylori resides in the gastric lumen and is a significant risk factor for gastritis and gastric cancer. This organism promotes apoptosis of gastric epithelial cells that are subsequently cleared by local phagocytes. C1q, the recognition component of the complement cascade, is an important molecule in immune regulation where it promotes uptake of apoptotic cells and modulates inflammation. We demonstrated that H pylori infection induces apoptosis of gastric AGS cells in vitro and that apoptotic epithelial cells are recognized and engulfed by macrophages independent of the method of cell death. Further, C1q binds to apoptotic cells and is important in the interaction between apoptotic cells and macrophages. We show that the absence of serum reduced attachment of AGS cells to phagocytes by up to 90% and the addition of 40μg/ml of C1q was sufficient to restore normal binding. A comparable effect of C1q on internalization of AGS cells was observed using a flow cytometric assay. C1q, in the absence of serum, attenuated IL-6, TNF-α and IL-1β production induced by 100 ng/ml of LPS or 100 MOI H. pylori compared to controls (45-60% reductions). In conclusion, we show that C1q is important in the resolution of inflammation by facilitating the engulfment of apoptotic cells and inhibiting the pro-inflammatory cytokine responses. Further, the inhibition of host responses attributed to the engulfment of apoptotic cells may be induced by extracellular factors including C1q.