Expression of the gastric H/K-ATPase alpha-subunit in the thymus may explain the dominant role of the beta-subunit in the pathogenesis of autoimmune gastritis.
The two subunits of the gastric H/K ATPase, namely the catalytic alpha-subunit and the glycoprotein beta-subunit, are the major targets of parietal cell autoantibodies associated with human and murine autoimmune gastritis. The murine disease induced by neonatal thymectomy is T cell-mediated. We have previously shown that transgenic expression of the H/K ATPase beta-subunit gene in the thymus prevented the development of autoimmune gastritis induced by thymectomy. However, little is known of the contribution of the H/K ATPase alpha-subunit in disease development. Here, we show that (1) in contrast to the gastric H/K ATPase beta-subunit, the alpha-subunit gene is expressed in normal BALB/c thymus. (2) transgenic expression of the gastric H/K ATPase alpha-subunit gene in the thymus failed to prevent the development of autoimmune gastritis and (3) normal BALB/c and transgenic mice expressing the alpha-subunit in the thymus develop autoimmune gastritis following immunisation with purified murine gastric H/K ATPase, whereas transgenic mice expressing the beta-subunit in the thymus do not. We propose that the expression of the H/K ATPase alpha-subunit in the normal thymus may account for the predominant role of the beta-subunit in the development of autoimmune gastritis induced either by thymectomy or by immunisation with the ATPase.
Alderuccio
F
F
Department of Pathology and Immunology, Monash University Medical School, Alfred Hospital, Melbourne, Australia. franka@cobra.path.monash.edu.au
Gleeson
P A
PA
Berzins
S P
SP
Martin
M
M
Van Driel
I R
IR
Toh
B H
BH
D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology* / Q000276:immunology; D005756:Gastritis / Q000201:enzymology* / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013270:Stomach / Q000201:enzymology; D013329:Structure-Activity Relationship; D013950:Thymus Gland / Q000201:enzymology*
D017506:H(+)-K(+)-Exchanging ATPase