Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not.
Carboxypeptidase R (EC 3.4.17.20; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity. Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation. CPN, however, previously termed kininase I and anaphylatoxin inactivator, is present in a stable active form in plasma. We report here the isolation of mouse proCPR and CPN cDNA clones that can induce their respective enzymatic activities in culture supernatants of transiently transfected cells. Potato carboxypeptidase inhibitor can inhibit carboxypeptidase activity in culture medium of mouse proCPR-transfected cells. The expression of proCPR mRNA in murine liver is greatly enhanced following LPS injection, whereas CPN mRNA expression remains unaffected. Furthermore, the CPR activity in plasma increased 2-fold at 24 h after LPS treatment. Therefore, proCPR can be considered a type of acute phase protein, whereas CPN is not. An increase in CPR activity may facilitate rapid inactivation of inflammatory mediators generated at the site of Gram-negative bacterial infection and may consequently prevent septic shock. In view of the ability of proCPR to also inhibit fibrinolysis, an excess of proCPR induced by LPS may contribute to hypofibrinolysis in patients suffering from disseminated intravascular coagulation caused by sepsis.
Sato
T
T
Department of Molecular Biology, Nagoya City University Medical School, Nagoya, Japan.
Miwa
T
T
Akatsu
H
H
Matsukawa
N
N
Obata
K
K
Okada
N
N
Campbell
W
W
Okada
H
H
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000201:enzymology; D001121:Lysine Carboxypeptidase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D000209:Acute-Phase Proteins; D018076:DNA, Complementary; D004792:Enzyme Precursors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D001121:Lysine Carboxypeptidase