Title:MALT Lymphoma, Stress Ulcer and Cholinergic Nerves from the Viewpoint of Bilateral and Unilateral Truncal Vagotomy and Substance P
Volume: 24
Issue: 18
Author(s): Yosuke Kodama, Kazuki Sasaki, Futa Murasato, Anders Overby, Shinichi Takahashi, Somay Y. Murayama, Hidenori Matsui and Masahiko Nakamura*
Affiliation:
- School of Pharmacy, Kitasato University, Tokyo,Japan
Keywords:
Restraint-induced ulcer, gastric MALT lymphoma, bilateral truncal vagotomy, unilateral truncal vagotomy, Helicobacter
heilmannii, cholinergic nerve, acetylcholinesterase, substance P, neurokinin-1 receptor.
Abstract: Background: Vagal nerve plays an important role in the stomach function. The cholinergic nerves are
the most abundantly distributed nerves in the gastric tissue. It has recently been reported that the vagal nerve is
significantly related to both gastric cancer development and progression. However, its relation to the mesenchymal
tumor, including MALT lymphoma, is not known. In this study, we investigated the effect of unilateral truncal
vagotomy on gastric MALT lymphoma development by using Helicobacter heilmannii-infected mouse model
as well as that of bilateral truncal vagotomy on stress-induced ulcer formation.
Methods: In the first part of this study, the distribution of the cholinergic nerves in the rat gastric mucosa and the
effect of bilateral truncal vagotomy, as well as various kinds of agents acting on autonomic nerves in rats, were
investigated by the histochemical and macroscopic method. In the second part, we employed MALT lymphoma
formation in C57BL/6NCrl mice that were infected with Helicobacter heilmannii. A total of 38 infected mice
underwent unilateral vagotomy under microscopy. The mice were randomized into 4 groups from which samples
were collected; 2, 3, 4 and 6 months after infection. Both the anterior and posterior sides of the stomachs were
sampled from each mouse for pathological and immunohistochemical analyses.
Results: The bilateral truncal vagotomy significantly suppressed the restraint-induced gastric ulcer formation in
rats, while bethanechol, and 6-hydroxydopamine led to an increase of the gastric ulcer formation. In the unilateral
truncal vagotomy study using MALT lymphoma, the thickness of the gastric mucosa was reduced in the
vagotomized side compared to the non-vagotomized side. Furthermore, the gastric MALT lymphoma was more
prominently found in the vagotomized anterior side of stomach compared with that in the non-vagotomized posterior
side of stomach. Substance P-immunoreactive nerves markedly increased surrounding the MALT lymphoma
and the neurokinin-1 receptor immunoreactive lymphocytes increased within the MALT lymphoma in the
vagotomized side. In conclusion, vagotomy enhanced gastric MALT lymphoma development possibly through
the substance P-neurokinin-1 receptor pathway.