|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Veterinary Pharmacology, The University of Tokyo, Tokyo, Japan
2 Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
3 National Institute of Animal Health, Tsukuba, Japan
4 Veterinary Public Health, The University of Tokyo, Tokyo, Japan
5 Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
* To whom correspondence should be addressed. E-mail: aozaki{at}mail.ecc.u-tokyo.ac.jp.
Endothelin
receptor null rats (ETB (-/-)) are a model for long segment Hirschsprung's disease. These
animals have significant intestinal distention (megaileum) proximal to a constricted
region of the GI tract lacking enteric ganglia. Experiments were performed to determine
the pathophysiological changes that occur in these animals and to examine the tunica
muscularis as a unique, immunologically active compartment. We observed abnormal
intestinal flora in ETB (-/-) rats that included a marked increase in Gram (-) aerobes
(Enterobacteriaceae) and anaerobes (Bacteroidaceae) in the distended region of the small
intestine. Histochemical observations showed that neutrophilic infiltration was rarely or
not observed, but the number of ED2 positive macrophages was increased in the tunica
muscularis. Expression of IL-1
and IL-6 mRNA was also significantly increased, and
the level of CD14 (LPS receptors) were increased significantly in the tunica muscularis.
Spontaneous phasic contractions were irregular in the distended intestinal regions of ETB
(-/-) rats and this was associated with an increased number of macrophages and damage to
interstitial cells of Cajal (ICC), as revealed using Kit-like immunoreactivity and electron
microscopy. These results suggest that ED2-positive resident macrophages may play an
important role in the inflammation of tunica muscularis in ETB (-/-) rats. Increased
numbers and activation of macrophages may result in damage to ICC networks leading to
disordered intestinal rhythmicity in regions of the gut where myenteric ganglia are intact.
This article has been cited by other articles:
![]() |
M. Hori, H. Nobe, K. Horiguchi, and H. Ozaki MCP-1 targeting inhibits muscularis macrophage recruitment and intestinal smooth muscle dysfunction in colonic inflammation Am J Physiol Cell Physiol, February 1, 2008; 294(2): C391 - C401. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Ohama, M. Hori, E. Momotani, Y. Iwakura, F. Guo, H. Kishi, S. Kobayashi, and H. Ozaki Intestinal inflammation downregulates smooth muscle CPI-17 through induction of TNF-{alpha} and causes motility disorders Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1429 - G1438. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Nakayama, K. Shimono, H.-N. Liu, H. Jiko, N. Katayama, T. Tomita, and K. Goto Pacemaker phase shift in the absence of neural activity in guinea-pig stomach: a microelectrode array study J. Physiol., November 1, 2006; 576(3): 727 - 738. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |