DIFFERENT SUSCEPTIBILITY OF MICE TO IMMUNE-MEDIATED CHOLANGITIS INDUCED BY IMMUNIZATION WITH CARBONIC-ANHYDRASE-II

Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of c arbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune ch olangitis have been reported to have serum antibodies to CA-II. Moreov er, active immunization of susceptible mice with CA-II results in infl ammation of submandibular glands, where CA-II is also expressed. In th e present study, we attempted to produce cholangitis by immunization w ith CA-II using two strains of mice with different potential susceptib ilities. Balb/c and DBA/1J mice were immunized with a dose of human CA -II (100 mu g) intraperitoneally every other week on three occasions. One week after the final immunization, mice were killed and blood and tissue samples harvested. Light and electron microscopic evaluation fo r inflammation was performed under coded identification. After immuniz ation of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between chola ngiocytes was also seen. Inflammation was not observed outside the liv er. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 1 5 Balb/c mice and in 3 (20%) of 15 DBA/1J mice. In the control mice im munized with bovine serum albumin (BSA), cholangitis was observed in o nly 1 (6.7%) of 15 Balb/c mice and none of 15 DBA/1J mice. Balb/c mice immunized with CA-II had statistically significant cholangitis compar ed with those immunized with BSA (p < 0.01), whereas DBA/1J did not sh ow a significant difference from controls. Balb/c mice immunized with CA-II showed specific antibody production after immunization, whereas DBA/1J mice immunized with CA-II had anti-CA-II antibody even in preim mune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/ c mice resulted in cholangitis in two (66.7%) of three Balb/c recipien ts. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.