Procarboxypeptidase R deficiency causes increased lethality in concanavalin A-induced hepatitis in female mice.
Carboxypeptidase R (CPR), also known as thrombin-activatable fibrinolysis inhibitor (TAFI), is an enzyme generated by proteolytic cleavage of its zymogen (proCPR). CPR removes the C-terminal arginine from inflammatory peptides such as C3a and C5a, bradykinin, enkephalin, and the thrombin-cleaved N-terminal fragment osteopontin (cleaved N-OPN). In the mouse model of concanavalin A (Con A)-induced immune-mediated fulminating hepatitis, cleaved N-OPN is one of the important peptides that induce the production of chemokines or cytokines. In the current study using proCPR deficient mice, we showed that injection of Con A into the mouse tail vein can induce a significantly higher lethality in proCPR-deficient female but not in male mice. Furthermore, a lack of CPR activity increased serum macrophage inflammatory protein-2 (MIP-2) and high-mobility group box 1 (HMGB1) levels after Con A injection. These in vivo findings suggest that CPR helps to protect against Con A-induced hepatitis.
Asai
Suzuka
S
Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Kimbara
Noriaki
N
Tada
Toyohiro
T
Imai
Masaki
M
Campbell
William
W
Okada
Hidechika
H
Okada
Noriko
N
D000818:Animals; D025901:Carboxypeptidase B2 / Q000172:deficiency*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology*; D018925:Chemokines / Q000097:blood; D003208:Concanavalin A / Q000633:toxicity*; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice
D018925:Chemokines; D016207:Cytokines; D003208:Concanavalin A; D025901:Carboxypeptidase B2