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

doi:10.1016/S0016-5085(98)70581-5

Gastroenterology

Volume 114, Issue 4, April 1998, Pages 675-689

https://doi.org/10.1016/S0016-5085(98)70581-5 Get rights and content

Abstract

Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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.

GASTROENTEROLOGY 1998;114:675-689

Section snippets

Animals

Specific pathogen–free female mice (6 weeks old) representing four inbred strains (C57BL/6, BALB/c, C3H/HeJ, and SV129) were purchased from Taconic Farms (Germantown, NY). Animals were housed in microisolator, solid-bottomed polycarbonate cages and fed a commercially prepared pelleted diet and given water ad libitum. The mice were all maintained in an American Association for Accreditation of Laboratory Animal Care–approved facility under barrier conditions as virus antibody free mice for the

H. felis infection results in greater inflammation and hyperplasia in C57BL/6 mice

Argyrophilic bacteria morphologically consistent with H. felis were observed in sections stained with Warthin–Starry in all H. felis–inoculated mice. The density of bacterial colonization within glands of the antrum and the corpus was scored 0–4, based on the size and frequency of aggregated bacteria within the glands. The antrum was consistently more heavily colonized than the corpus in all infection groups, regardless of mouse strain or duration of infection. Bacterial colonization of the

Discussion

Our study shows that H. felis infection leads to increased gastric mucosal proliferation and apoptosis in C57BL/6 mice and, over time, results in an expansion of a SP-positive mucous cell lineage, along with a marked decline in both parietal and chief cells. The changes in these cell lineages in C57BL/6 mice were shown by immunocytochemical staining, toluidine blue thin sections, and electron-microscopic studies. Similar changes were not observed in either the BALB/c or C3H/HeJ mouse strains.

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^☆: Address requests for reprints to: Timothy C. Wang, M.D., Gastrointestinal Unit, GRJ 724 Massachusetts General Hospital, 32 Fruit Street, Boston, Massachusetts 02114. e-mail: [email protected]; fax: (617)-726-3673.

^☆☆: Supported by grant RO1 CA67529 from the National Institutes of Health.

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Alimentary TractMice lacking secretory phospholipase A2 show altered apoptosis and differentiation with Helicobacter felis infection☆,☆☆

Abstract

Section snippets

Animals

H. felis infection results in greater inflammation and hyperplasia in C57BL/6 mice

Discussion

Gastroenterology

Gastroenterology

Cell

Cell

J Biol Chem

J Biol Chem

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterol Clin North Am

J Biol Chem

J Biol Chem

Gastroenterology

FEBS Lett

Gastroenterology

Biochem Biophys Res Commun

Gastroenterology

Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia

J Clin Invest

A human model of gastric carcinogenesis

Cancer Res

Local and systemic immune responses in murine Helicobacter felis active chronic gastritis

Infect Immun

Use of a mouse model to examine anti–Helicobacter pylori agents

Scand J Gastroenterol

Role of the host in pathogenesis of Helicobacter-associated gastritis: H. felis infection of inbred and cogenic mouse strains

Infect Immun

Atrophic gastric changes in both Helicobacter felis and Helicobacter pylori infected mice are host dependent and separate from antral gastritis

Gut

Identifying and counting epithelial cell types in the corpus of the mouse stomach

Anat Rec

Alimentary Tract
Mice lacking secretory phospholipase A₂ show altered apoptosis and differentiation with Helicobacter felis infection☆,☆☆