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Potential role of bacterial lipopolysaccharides in the development of autoimmune gastritis induced by neonatal thymectomy

Department of Molecular Pharmacology, School of Pharmaceutical Sciences Kitasato University, Tokyo, Japan

Tatsuya Mizoroki

Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan

Hideyo Shimada

Division of Pathophysiology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan

Kunio Ishii

Department of Molecular Pharmacology, School of Pharmaceutical Sciences Kitasato University, Tokyo, Japan

Masamichi Hosono

Department of Cell Biology, Graduate School of Science and Technology, Niigata University, Niigata, Japan

Yoshio Kumazawa

Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan, kumazawa{at}jet.sci.kitasato-u.ac.jp

The role of LPS in the development of autoimmune gastritis (AIG) in BALB/c mice thymectomized on day 3 after birth (d3-Tx) was investigated in LPS-non-responder BALB/lps ^d mice. The symptoms were classified into three types: (i) hypertrophic stomach (HS) and lymphocyte infiltration (LI)-double negative; (ii) HS-negative and LI-positive; and (iii) HS- and LI-double positive. The double positive type-3 was termed AIG. Following d3-Tx, LPS-responder BALB/c (Lps ⁿ) mice showed the following incidence: type-1 (14%), type-2 (14%) and type-3 (72%). In contrast, the incidence in BALB/lps^d mice was 67%, 22% and 11%, respectively. Thus the frequency of AIG development in BALB/lps^d mice was much lower than in BALB/c mice. A single administration of LPS on day 2 post-d3-Tx induced severe AIG incidence in all d3-Tx BALB/c mice but not in d3-Tx BALB/lps^d mice, suggesting that LPS influences the progression of AIG development. Formation of auto-antibodies against the proton pump (H⁺/K⁺-ATPase) seemed to be related to AIG incidence in d3-Tx BALB/c mice. In d3-Tx BALB/lps^d mice, however, higher levels of auto-antibodies were detected in the type-2 mice, whereas AIG incidence was much lower than that in d3-Tx BALB/c mice. Thus, formation of auto-antibodies against the proton pump in d3-Tx BALB/lps ^d mice does not appear to correlate with AIG pathogenesis.

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