Mice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection.

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.