Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II

Yoshiyuki Ueno, Motoyasu Ishii, Satoru Takahashi, Takehiko Igarashi, Takayoshi Toyota, Nicholas F La Russo

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100μg) 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 for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 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 compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show 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 preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.

Original languageEnglish (US)
Pages (from-to)629-637
Number of pages9
JournalLaboratory Investigation
Volume78
Issue number5
StatePublished - May 1998

Fingerprint

Carbonic Anhydrase II
Cholangitis
Immunization
Inbred DBA Mouse
Bovine Serum Albumin
Inflammation
Adoptive Transfer
Antibodies
Submandibular Gland
Liver
Bicarbonates
Bile Ducts
Serum
Carbon Dioxide
Antibody Formation
Protons

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II. / Ueno, Yoshiyuki; Ishii, Motoyasu; Takahashi, Satoru; Igarashi, Takehiko; Toyota, Takayoshi; La Russo, Nicholas F.

In: Laboratory Investigation, Vol. 78, No. 5, 05.1998, p. 629-637.

Research output: Contribution to journalArticle

Ueno, Yoshiyuki ; Ishii, Motoyasu ; Takahashi, Satoru ; Igarashi, Takehiko ; Toyota, Takayoshi ; La Russo, Nicholas F. / Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II. In: Laboratory Investigation. 1998 ; Vol. 78, No. 5. pp. 629-637.
@article{d3fcf1d0c9464fcea17fb2d099ab6808,
title = "Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II",
abstract = "Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100μg) 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 for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3{\%}) of 15 Balb/c mice and in 3 (20{\%}) of 15 DBA/1J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 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 compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show 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 preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7{\%}) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.",
author = "Yoshiyuki Ueno and Motoyasu Ishii and Satoru Takahashi and Takehiko Igarashi and Takayoshi Toyota and {La Russo}, {Nicholas F}",
year = "1998",
month = "5",
language = "English (US)",
volume = "78",
pages = "629--637",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Different susceptibility of mice to immune-mediated cholangitis induced by immunization with carbonic anhydrase II

AU - Ueno, Yoshiyuki

AU - Ishii, Motoyasu

AU - Takahashi, Satoru

AU - Igarashi, Takehiko

AU - Toyota, Takayoshi

AU - La Russo, Nicholas F

PY - 1998/5

Y1 - 1998/5

N2 - Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100μg) 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 for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 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 compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show 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 preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.

AB - Carbonic anhydrase II (CA-II), an enzyme that catalyzes hydration of carbon dioxide to bicarbonate and hydrogen ions, is located exclusively in cholangiocytes in the liver. Recently, patients with autoimmune cholangitis have been reported to have serum antibodies to CA-II. Moreover, active immunization of susceptible mice with CA-II results in inflammation of submandibular glands, where CA-II is also expressed. In the present study, we attempted to produce cholangitis by immunization with CA-II using two strains of mice with different potential susceptibilities. Balb/c and DBA/1J mice were immunized with a dose of human CA-II (100μg) 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 for inflammation was performed under coded identification. After immunization of Balb/c mice, numerous mononuclear cells, mostly CD4-positive T cells, appeared around bile ducts; lymphocyte invasion between cholangiocytes was also seen. Inflammation was not observed outside the liver. Morphologic evidence of cholangitis was observed in 8 (53.3%) of 15 Balb/c mice and in 3 (20%) of 15 DBA/1J mice. In the control mice immunized with bovine serum albumin (BSA), cholangitis was observed in only 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 compared with those immunized with BSA (p < 0.01), whereas DBA/1J did not show 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 preimmune sera. Adoptive transfer of splenocytes from CA-II-immunized Balb/c mice resulted in cholangitis in two (66.7%) of three Balb/c recipients. These data strongly suggest that the cholangitis can be induced by CA-II immunization in susceptible strains of mice.

UR - http://www.scopus.com/inward/record.url?scp=0031834730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031834730&partnerID=8YFLogxK

M3 - Article

C2 - 9605187

AN - SCOPUS:0031834730

VL - 78

SP - 629

EP - 637

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 5

ER -