Human angiogenin (ANG), better known for its proposed link with angiogenesis and as a promoter of tumour growth, has several unusual properties that indicated to researchers that its main function was something other than vascular development. In fact, observations that inflammation leads to an increase in the level of expression of messenger RNA encoding ANG and that members of the angiogenin family are subject to high rates of mutation both indicated that these molecules might contribute in some way to defending the host.
Using germ-free mice, the authors used microarrays to identify host genes that showed an increased level of expression in response to colonization of the small intestine by Bacteroides thetaiotaomicron, a member of the normal intestinal microflora. One molecule that emerged from this analysis was a previously uncharacterized member of the angiogenin family, Ang4. Further analysis showed that this molecule is expressed and secreted by Paneth cells and that normal intestinal bacteria induce its expression. The authors also showed that Ang4 has bactericidal activity against enteric pathogenic bacteria, including Enterococcus faecalis and Listeria monocytogenes. By contrast, the related family members mouse Ang1 and human ANG, which appear in the circulation during the acute-phase response to infection, have bactericidal and fungicidal activities against pathogens that are known to cause systemic infections. Interestingly, these molecules have little activity against enteric pathogens, which indicates that whereas Ang4 is a mediator of epithelial host defence in the intestine, Ang1 and ANG are unappreciated components of the systemic response to infection.
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