Influence of humoral immunoreaction on hepatic nonparenchymal cells in ex situ xenoperfused rat livers.
BACKGROUND
The influence of xenogeneic humoral immunoreaction on hepatic nonparenchymal cells (NPCs) was evaluated ex situ in xenoperfused rat livers.


METHODS
Isolated rat livers were perfused via the portal vein (PV) for 240 min. The perfusates consisted of fresh rat blood (group 1), fresh human blood (group 2), and fresh human blood containing 5 microg/mL soluble complement receptor type 1 (Group 3).


RESULTS
Deposition of human IgM and C(5b-9) complement was observed in group 2, although only human IgM deposition was detected in group 3. Portal vein pressure in group 2 rose drastically during the first 10 min. Creatine kinase BB component gradually increased in all groups, followed by an elevation in alanine aminotransferase and both parameters were significantly higher in group 2 than in groups 1 and 3. In group 2, platelet thrombi in the peripheral PVs and periportal hemorrhage were observed after 10 min, and massive necrosis around the central veins after 240 min; these changes were not observed in group 1 or 3. Production of tumor necrosis factor alpha and alpha interferon and expression of intercellular adhesion molecule 1 (ICAM-1) were lower in group 2 than in groups 1 and 3. In group 2, there were negative areas for ICAM-1 and tumor necrosis factor alpha staining around the central veins after 240 min, which were consistent with necrotic areas.


CONCLUSIONS
In xenoperfused rat livers, humoral mediators initially caused the disturbance of microcirculation, which would induce long ischemia in the pericentral areas, resulting in massive necrosis. NPC necrosis may be responsible for less production of cytokines and adhesion molecules in the xenoperfused livers.
Uesugi
T
T
Department of Gastroenterological Surgery, Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Ikai
I
I
Satoh
S
S
Yagi
T
T
Kanazawa
A
A
Takeyama
O
O
Nishitai
R
R
Okabe
H
H
Katsura
N
N
Terajima
H
H
Takahashi
R
R
Yamaoka
Y
Y
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D003402:Creatine Kinase / Q000378:metabolism; D052276:Creatine Kinase, BB Form; D019040:E-Selectin / Q000235:genetics / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D008102:Liver Circulation / Q000276:immunology; D008297:Male; D008833:Microcirculation / Q000276:immunology; D009336:Necrosis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011951:Receptors, Complement / Q000276:immunology; D013925:Thromboplastin / Q000235:genetics / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D000910:Antibodies, Heterophile; D019040:E-Selectin; D007375:Interleukin-1; D007527:Isoenzymes; D012333:RNA, Messenger; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013925:Thromboplastin; D000410:Alanine Transaminase; D003402:Creatine Kinase; D052276:Creatine Kinase, BB Form