arginine consumption by the intestinal parasite giardia intestinalis reduces proliferation of intestinal epithelial cells精氨酸消耗肠道寄生虫鞭毛虫intestinalis减少肠上皮细胞增殖.pdfVIP

Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells 1 ´ 2 3 ¨ 1 Britta Stadelmann *, Marıa C. Merino , Lo Persson , Staffan G. Svard ´ ´ 1 Department of Cell and Molecular Biology, Biomedical Centre Uppsala, University of Uppsala, Uppsala, Sweden, 2 Instituto de Investigacion Medica Mercedes y Martin ´ Ferreyra-Conicet, Cordoba, Argentina, 3 Department of Experimental Medical Science, Biomedical Centre Lund, University of Lund, Lund, Sweden Abstract In the field of infectious diseases the multifaceted amino acid arginine has reached special attention as substrate for the hosts production of the antimicrobial agent nitric oxide (NO). A variety of infectious organisms interfere with this part of the host immune response by reducing the availability of arginine. This prompted us to further investigate additional roles of arginine during pathogen infections. As a model we used the intestinal parasite Giardia intestinalis that actively consumes arginine as main energy source and secretes an arginine-consuming enzyme, arginine deiminase (ADI). Reduced intestinal epithelial cell (IEC) proliferation is a common theme during bacterial and viral intestinal infections, but it has never been connected to arginine-consumption. Our specific question was thereby, whether the arginine-consumption by Giardia leads to reduced IEC proliferation, in addition to NO reduction. In vitro cultivation of human IEC lines in arginine-free or arginine/ citrulline-complemented medium, as well as in