Hepatitis induced by an IgM monoclonal antibody against procarboxypeptidase R.
Procarboxypeptidase R (proCPR), also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is present in plasma and can be activated to carboxypeptidase R (CPR) by trypsin-like enzymes such as thrombin and plasmin. CPR has the carboxypeptidase B-like activity that can inactivate the inflammatory peptides such as C5a by removing the C-terminal arginine and can interfere with fibrinolysis by removing C-terminal lysine residue of fibrin. In the present study, we conducted to produce monoclonal antibodies (mAbs) by using spleen cells from proCPR-deficient mice immunized by partially purified mouse proCPR. The mAbs obtained were IgM isotype and reacted with proCPR and interfered with activation of proCPR to CPR by thrombin-thrombomodulin complex. Some BALB/c mice implanted with the hybridoma died in 7 days, and intravenous injection of the mAb to BALB/c mice induced transient elevation of GOT and GPT in plasma although injection to the deficient mice did not. Furthermore, the histological features showed the focally lesions in liver tissue of BALB/c mice injected with the mAb. Since liver is the major site of proCPR synthesis, IgM mAb to proCPR should have induced local inflammation at the side resulting in induction of hepatitis.
He
Lianying
L
Department of Biodefense, Nagoya City University Graduate School of Medical Sciences, Aichi 467-8601, Japan.
Asai
Suzuka
S
Kawamura
Takeshi
T
Kimbara
Noriaki
N
Tada
Toyohiro
T
Okada
Hidechika
H
Okada
Noriko
N
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology* / Q000302:isolation & purification; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D025901:Carboxypeptidase B2 / Q000037:antagonists & inhibitors / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006505:Hepatitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D008099:Liver / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D025901:Carboxypeptidase B2