Ron receptor tyrosine kinase-dependent hepatic neutrophil recruitment and survival benefit in a murine model of bacterial peritonitis.

Critical Care Medicine
Charles C CaldwellS E Waltz

Abstract

To determine whether Ron receptor tyrosine kinase signaling affects the in vivo response to bacterial peritonitis. Experimental study. University laboratory. Male mice 8-11 wks of age (22-28 g). A genetic approach comparing wild-type mice to mice with a targeted deletion of the Ron tyrosine kinase signaling domain (TK-/-) was undertaken to determine the influence of Ron receptor in the in vivo response to a well-characterized model of bacterial peritonitis and sepsis induced by cecal ligation and puncture. Several clinical (i.e., survival curves, blood and tissue bacterial burdens, and neutrophil oxidative burst), morphologic (i.e., liver histology and leukocyte trafficking), and biochemical variables (i.e., serum aminotransferases and select serum cytokine and chemokine levels) important for assessing inflammatory responses to bacterial infection were assessed in mice following cecal ligation and puncture. Ron TK-/- mice had a significant decrease in survival time compared with controls, and this was associated with a significant increase in bacterial colony-forming units found in the blood and several end-organs. Moreover, this increased bacterial load was associated with increased liver necrosis and serum alanine aminotransf...Continue Reading

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