Immunohistochemical Analysis of the Pathogenicity of Helicobacter pylori Infection: Excess Nitric Oxide Induced Indirectly by Lewis X and Y is the Cause of the Pathogenicity of Helicobacter pylori Infestation in the Stomach

Inducible nitric oxide synthase (iNOS) is expressed in the germinal centers (GCs) of mucosa-associated lymphoid tissue (MALT) and regional lymph nodes (RLNs) in the stomachs of patients with Helicobacter pylori (HP)-related ulcer. This study used immunohistochemistry to deduce how the iNOS was expressed and what the iNOS induced on the MALT in four cases. HP bodies were labeled with anti-HP, anti-Lewis X and Y, and anti-IgH antibodies in the surface mucous coat and in the glands. Lewis X or Y was detected in regenerative, metaplastic and atrophic glandular epithelial cells and GCs of RLNs. The expression of iNOS was recognized again in some glandular epithelial cells and in the GCs of the MALT and RLNs. The developed MALT included many IgM + CD5 - cells in the background of an ordinary mucosal immunity. Pseudonodular growth of the IgM + CD5 - cells was recognized in one case. It is suggested that Lewis X and Y from HP bodies induced iNOS in the GCs. Dominant IgM + CD5 - cells in the MALT suggested that excess nitric oxide (NO) produced by iNOS disturbed anti-HP B-cell immunity development in the GCs. As NO is also a mutagen, the IgM + CD5 - B-cells' pseudonodular growth might explain MALT-type lymphomagenesis.