Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis
that may progress to atrophic gastritis, a premalignant process. A mouse model of
Helicobacter felis infection was used to study possible genetic determinants of the
response to infection.
Three inbred mouse strains with known secretory phospholipase A2 (sPLA2) genotypes
[BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (-/-)] were orally infected with H. felis
and examined longitudinally using routine histology, immunocytochemistry, electron
microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies.
Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis
in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal
and chief cells, along with a marked expansion of an aberrant gastric mucous cell
lineage that stained positive for spasmolytic polypeptide. In contrast, no significant
change in these cell types was observed in BALB/c and C3H/HeJ strains. Increased expression
of sPLA2 was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA2
expression was absent in C57BL/6 mice.
H. felis infection leads to increased apoptosis and altered cellular differentiation
in the C57BL/6 mouse, a strain that lacks gastric sPLA2 expression. Because sPLA2
has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp
formation in the colon, these studies suggest that sPLA2 may also influence the gastric
epithelial response to Helicobacter infection.