Mucosal ornithine decarboxylase, polyamines, and hyperplasia in infected intestine

Abstract

Ornithine decarboxylase (ODC), through the regulation of polyamine biosynthesis, influences normal mucosal growth and cell proliferation. The purpose of our study was to determine whether mucosal ODC activity and polyamines play a role in the dramatic increase in mucosal mass and crypt elongation associated with parasite-induced inflammation in the small intestine. Rats were inoculated orally with L1 larvae of the parasitic nematode Trichinella spiralis and killed at different times during the enteric phase of infection. Duodenal and jejunal mucosal ODC activities increased significantly from 2 to 14 days, peaking 7 days postinfection (PI). By 21 days PI, enzyme activity had returned to near normal values. In the ileal mucosa, ODC activity was increased only at 7 days PI. Increases in ODC activity were paralleled by increases in mucosal putrescine, spermidine, and spermine content. Infection with T. spiralis induced DNA synthesis and evoked a significant rise in DNA, RNA, and protein content in the mucosa. Increases in nucleic acid and protein levels were most prominent in the proximal half of the small intestine where the majority of worms reside. Treatment of rats with alpha-difluoromethylornithine (DFMO) prevented the infection-induced elevations in mucosal ODC activity, polyamine levels, DNA synthesis, and DNA, RNA, and protein content without influencing the development of inflammation or the parasite's life cycle. These results suggest that mucosal hyperplasia caused by infection may be regulated, in part, by the growth-promoting effects of ODC, presumably through the stimulation of crypt cell proliferation. Thus ODC may be an important determinant of the intestinal response to infection.