Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not
Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not
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DOI：
10.4049/jimmunol.165.2.1053
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发表时间：
2000-07-15
影响因子：
4.4
通讯作者：
Okada, H
中科院分区：
文献类型：
--
作者：
Sato, T;Miwa, T;Okada, H
羧基肽酶R （EC 3.4.17.20； CPR）和羧基肽酶N （EC 3.4.17.3； CPN）可从具有生物活性的肽如激肽和过敏毒素中切割羧基末端精氨酸和赖氨酸残基，从而调节其生物活性。人proCPR，也被称为凝血酶活化纤维蛋白溶解抑制剂，血浆前羧肽酶B和原羧肽酶U，是一种在凝血过程中被激活的血浆酶原。然而，CPN，以前被称为激酶I和过敏毒素灭活剂，在血浆中以稳定的活性形式存在。我们在这里报道了小鼠proCPR和CPN cDNA克隆的分离，这些克隆可以在瞬时转染细胞的培养上清液中诱导它们各自的酶活性。马铃薯羧肽酶抑制剂可以抑制小鼠procpr转染细胞的培养基中羧肽酶的活性。注射LPS后，小鼠肝脏中proCPR mRNA的表达显著增强，而CPN mRNA的表达不受影响。此外，LPS处理后24小时血浆中CPR活性增加2倍。因此，proCPR可以被认为是一种急性期蛋白，而CPN不是。CPR活性的增加可能促进革兰氏阴性细菌感染部位产生的炎症介质的快速失活，从而可能预防感染性休克。鉴于proCPR也具有抑制纤维蛋白溶解的能力，LPS诱导的proCPR过量可能导致脓毒症引起弥散性血管内凝血患者的低纤溶。
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 procarboxypeptidase 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.