Cholangiohepatitis and inflammatory bowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac:ICR:HascidfRF mice.

Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge 02139, USA.
Experimental Biology and Medicine (Impact Factor: 2.17). 06/2001; 226(5):420-8.
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Helicobacter bilis and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice. To determine the pathogenic potential of H. sp. in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:Icr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with approximately 3 x 10(7) colony-forming units (CFU) of H. sp. Mice were necropsied at various time points postinoculation (PI). Sham-inoculated mice had no clinical, gross, or histopathological lesions. In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI. A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bowel disease (IBD) and hepatitis in scid and immunocompetent A/J mice. These results provide a new model of IBD and cholangio-hepatitis associated with a specific urease-negative, novel H. species.

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    • "The bacterial pellet was resuspended in sterile PBS to a concentration of approximately 107 organisms ml−1 based on spectrophotometric examination. Using a previously published inoculation strategy, experimental mice (24 males, 24 females) received 0.2 ml inoculum by intraperitoneal injection, whilst control mice (8 males, 8 females) were given 0.2 ml sterile PBS (McCathey et al., 1999; Shomer et al., 2001). One mouse from each cage (total of two control and six experimental mice of each sex) was necropsied at 6 and 12 months after dosing; necropsies on the remaining mice were performed when the study was concluded at 18 months post-inoculation (p.i.). "
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