Carboxypeptidase R is an inactivator of complement-derived inflammatory peptides and an inhibitor of fibrinolysis.
Carboxypeptidase R (CPR) exists in precursor form (proCPR) in plasma in contrast to carboxypeptidase N (CPN), which is present in the active state. CPR plays two important roles, one of which appears to be the control of the inflammatory response by inactivation of anaphylatoxins such as complement-derived C3a and C5a. Therefore, an increase in CPR activity may facilitate rapid inactivation of these inflammatory mediators generated at the site of bacterial infection. Upregulation of proCPR expression during the inflammatory response initiated for instance by endotoxin (lipopolysaccharide) should play a role in suppressing hyper-reactivity as seen in septic shock. CPR also functions as an inhibitor of fibrinolysis, where its ability to prevent binding of plasminogen to lysine residues on fibrin clots significantly lengthens tissue plasminogen activator (tPA)-induced fibrinolysis time. Therefore, upregulation of proCPR production during the inflammatory response may exacerbate thrombosis contributing to the development of disseminated intravascular coagulation as well as other conditions involving thrombosis. Co-administration of tPA and a specific inhibitor of CPR, such as potato carboxypeptidase inhibitor, which does not affect CPN, may be useful in thrombolytic therapy.
Campbell
W
W
Choju Medical Institute, Fukushimura Hospital, Toyohashi, Japan.
Okada
N
N
Okada
H
H
D000706:Anaphylatoxins / Q000037:antagonists & inhibitors*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D015926:Complement C3a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D015195:Drug Design; D019446:Endotoxemia / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000378:metabolism; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D011817:Rabbits; D051381:Rats; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism; D015912:Thrombolytic Therapy; D018180:Thrombomodulin / Q000378:metabolism; D014162:Transfection
D000706:Anaphylatoxins; D004792:Enzyme Precursors; D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; D018180:Thrombomodulin; D015926:Complement C3a; D015936:Complement C5a; D025901:Carboxypeptidase B2