title: Intestinal platelet-activating factor synthesis during Nippostrongylus brasiliensis infection in the rat.
abstract: Infection of rats with the parasite Nippostrongylus brasiliensis results in severe intestinal pathology and dysfunction. Much of the damage that occurs within the intestinal tract may be the direct result of the production of potent inflammatory mediators. PAF is one such lipid mediator that may lead to the altered motility and secretory changes that occur during N. brasiliensis infection. Male, Sprague-Dawley rats were subcutaneously infected with 3000 third stage larvae, while control groups were injected with phosphate buffered saline. At various times post infection (4-42 days) groups of four or more infected and control rats were killed and samples of ileum and jejunum were removed for determination of PAF and leukotriene synthesis (LTB4 and LTC4), myeloperoxidase (MPO) activity and tissue eosinophil and mast cell numbers. Separate groups of rats were killed at similar times for the determination of intestinal worm burden and serum rat mast cell protease II (RMCP-II) levels. Significant elevation in PAF synthesis was not seen until day 15, a time when the intestinal worm burden was no longer evident. Furthermore, this elevation was restricted to the jejunum. The elevation in PAF synthesis correlated with a significant elevation in histologically detectable eosinophils and mast cells in the jejunum. Mast cell activity, as detected through serum concentrations of RMCP-II, was significantly elevated at day 8 post-infection and remained elevated until day 18 post-infection. However, despite significant changes in ileal eosinophil and mast cell numbers, PAF synthesis in the ileum did not differ significantly over the course of the infection. LTB4 and LTC4 production and MPO activity, were significantly elevated in both ileum and jejunum only following worm loss. These results demonstrate that PAF synthesis is altered following primary infection with N. brasiliensis. Changes in PAF synthesis paralleled changes in synthesis of other inflammatory mediators and were associated with hyperplasia of various inflammatory cells. Nevertheless, elevated PAF production is not simply a consequence of intestinal eosinophil and mast cell hyperplasia, as ileal PAF production did not significantly change despite hyperplasia of these cell types.
authors.affiliation: Gastrointestinal Sciences Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: A D
authors.initials: AD
authors.lastname: Befus
authors.forename: J L
authors.initials: JL
authors.lastname: Wallace
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D053818:Chymases; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D007082:Ileum / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology; D007583:Jejunum / Q000166:cytology / Q000378:metabolism* / Q000469:parasitology; D007975:Leukotriene B4 / Q000096:biosynthesis; D015289:Leukotrienes / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000502:physiology; D009349:Nematode Infections / Q000378:metabolism*; D009559:Nippostrongylus; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D015289:Leukotrienes; D010972:Platelet Activating Factor; D013189:SRS-A; D007975:Leukotriene B4; D009195:Peroxidase; D012697:Serine Endopeptidases; D053818:Chymases