Induction of a rat enteric defensin gene by hemorrhagic shock

Multicellular organisms utilize a battery of extracellular and cellular mec hanisms to defend against microbial infiltration. Among the armamentarium u sed by the small intestine to defend against microbial invasion are antimic robial peptides called defensins, We previously have shown that gut barrier function is impaired following hemorrhagic shock, resulting in translocati on of bacteria or endotoxin, Using a rat model, we examined the effect of h emorrhagic shock on alpha-defensin expression, We utilized the anchored rev erse transcriptase PCR strategy to isolate a rat enteric defensin cDNA, The cDNA is 406 bases in length and encodes a putative prepro-enteric defensin that we have named rat defensin 5 (RD-5). RD-5 expression is restricted to the small intestine and is specifically localized by in situ hybridization to the Paneth cells. A 10-fold increase in its steady state levels was obs erved in the distal intestine immediately after the termination of shock Th is is the first study to show that enteric defensins are inducible followin g injury. We suggest that enteric defensins may contribute to the complex a nd integrated barrier function of the intestinal mucosal surface.