In:
The Journal of Immunology, The American Association of Immunologists, Vol. 173, No. 7 ( 2004-10-01), p. 4669-4674
Abstract:
Carboxypeptidase R (CPR) is a heat-labile enzyme found in serum in addition to stable carboxypeptidase N. CPR cleaves the C-terminal basic amino acids, arginine and lysine, from inflammatory peptides such as complement C3a and C5a, bradykinin, and enkephalin. This enzyme is generated from procarboxypeptidase R (proCPR), also known as thrombin-activatable fibrinolysis inhibitor, following cleavage by proteolytic enzymes such as thrombin, plasmin, and trypsin. We generated proCPR-deficient mice by knocking out exons 4 and 5 of the proCPR gene, which are regarded as essential for CPR function. At LPS challenge, there was virtually no difference in lethality among proCPR+/+, proCPR+/−, and proCPR−/− mice. However, challenge with cobra venom factor, which can activate and deplete almost all complement in vivo, induced a lethal effect on proCPR−/− mice following LPS sensitization which up-regulates C5a receptor expression. In contrast, proCPR+/+ and proCPR+/− mice were able to tolerate the cobra venom factor challenge with the limited dose (30 U). Although carboxypeptidase N plays a role in inactivation of inflammatory peptides in vivo, CPR may also be important in the regulation of hyperinflammation.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.173.7.4669
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2004
detail.hit.zdb_id:
1475085-5
Permalink