The role of leucocytes in the induction of fluid secretion by Salmonella typhimurium.
Nitrogen mustard (N2M) treatment of rabbits induced neutropenia, and, in ligated ileal loops, it inhibited fluid secretion induced by salmonella or by cholera toxin (CT). Pretreatment of rabbits with indomethacin almost abolished salmonella-induced fluid secretion and significantly reduced that induced by CT. Similar effects of N2M and indomethacin on fluid secretion induced by salmonella, but not by CT, have been reported by other workers and used to implicate prostaglandins, from the salmonella-induced inflammation, as mediators of fluid secretion. In contrast, we show that N2M treatment, in addition to reducing CT-induced secretion, caused severe morphological alterations to ileal mucosa. Irradiation techniques were developed for inducing neutropenia, but they did not totally inhibit salmonella-induced leucocyte influx into ileal mucosa. We propose an alternative mechanism for the inhibitory effect of N2M on salmonella- and CT-induced secretion, based on the known anti-mitotic activity of N2M. Also, the anti-secretory effect of indomethacin cannot be attributed uniquely to its anti-inflammatory activity because it depressed CT-induced secretion as well as salmonella-induced secretion. These results support the concept of pathophysiological secretion in infectious diarrhoea, developed previously for rotavirus and extended to bacterial infections.
Department of Microbiology, University of Birmingham.
T S
TS
Wallis
A T
AT
Vaughan
G J
GJ
Clarke
G M
GM
Qi
K J
KJ
Worton
D C
DC
Candy
M P
MP
Osborne
J
J
Stephen
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002772:Cholera Toxin / Q000378:metabolism; D007082:Ileum / Q000648:ultrastructure*; D007213:Indomethacin / Q000494:pharmacology; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008026:Ligation; D008466:Mechlorethamine; D008855:Microscopy, Electron, Scanning; D009503:Neutropenia / Q000139:chemically induced; D011817:Rabbits; D012486:Salmonella typhimurium / Q000472:pathogenicity*
D008466:Mechlorethamine; D002772:Cholera Toxin; D007213:Indomethacin