FIG 6.

Evidence for positive-feedbacks loops in the intestine. (A) Effect of exogenous DNA with or without DNase I on uric acid formation in the lumen of the rabbit GI tract. Rabbit intestinal loops were left uninfected and were injected with 2 ml of DNase I alone, 2 ml of 100 μg/ml salmon DNA, or DNA plus DNase I. After 20 h, the uric acid concentration in the intestinal-loop fluid was assayed, showing that uric acid can be generated in vivo in the gut in the presence of DNA. (B) Feedback effects of uric acid on ATP release from HL-60 cells. Uric acid alone did not trigger a release of ATP from HL-60 cells, but it potentiated the ATP release triggered by exposure to hypotonic medium, which causes cell swelling. The hypotonic conditions used here were intended as a surrogate for physical stresses, such as mechanical stimulation, shear stress from liquid flow, or changes in pressure, as may occur in vivo. (C) Schematics showing positive-feedback loops that are hypothesized to occur in the GI tract. (Top) ATP released into the lumen as a result of infection is broken down to nucleosides, purines, and uric acid. However, since uric acid can itself enhance ATP release (B), a positive-feedback loop is formed. (Bottom) Uric acid can be formed from the breakdown of DNA, but uric acid also enhances the release of extracellular DNA from host cells (Fig. 3G), so another positive-feedback loop is created. The error bars indicate SD.