title: Procarboxypeptidase R deficiency causes increased lethality in concanavalin A-induced hepatitis in female mice.
abstract: 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.
authors.affiliation: Department of Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Suzuka
authors.initials: S
authors.lastname: Asai
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kimbara
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Tada
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.forename: William
authors.initials: W
authors.lastname: Campbell
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
mesh_terms: 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
chemical_list: D018925:Chemokines; D016207:Cytokines; D003208:Concanavalin A; D025901:Carboxypeptidase B2