CHEMERIN 158K IS THE DOMINANT CHEMERIN ISOFORM IN SYNOVIAL AND CEREBROSPINAL FLUIDS BUT NOT IN PLASMA.
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Lee, David and Leung, Lawrence (2011) CHEMERIN 158K IS THE DOMINANT CHEMERIN ISOFORM IN SYNOVIAL AND CEREBROSPINAL FLUIDS BUT NOT IN PLASMA. The Journal of biological chemistry, 286 (45). pp. 39520-39527. ISSN 0021-9258
Abstract
Chemerin is a chemoattractant involved in immunity that may also function as an
adipokine. Chemerin circulates as an inactive precursor (chem163S), and its activation requires proteolytic cleavages at its C-terminus, involving proteases involved in coagulation, fibrinolysis and inflammation. However the key proteolytic steps in prochemerin activation in vivo remain to be established. Previously we have shown that C-terminal cleavage of chem163S by plasmin to chem158K, followed by a carboxypeptidase cleavage leads to the most active isoform, chem157S. In order to identify and quantify the in vivo chemerin isoforms in biological specimens, we developed specific ELISAs for chem163S, chem158K, and chem157S, using antibodies raised against peptides from the C-terminus of the different chemerin isoforms. We found that the mean plasma concentrations of chem163S, chem158K and chem157S were 40±7.9, 8.1±2.9, and 0.7±0.8 ng/ml respectively. The total level of cleaved and non-cleaved chemerins in cerebrospinal fluids (CSF) was ~10% of plasma levels while it was ~2-fold elevated in synovial fluids from patients with arthritis. On the other hand, the fraction of cleaved chemerins was much higher in synovial fluid and CSF samples than in plasma (~75%, 50%, and 18% respectively). Chem158K was the dominant chemerin isoform and it was not generated by ex vivo processing, indicating that cleavage of prochemerin at position 158K, whether by plasmin or another serine protease, represents a major step in prochemerin activation in vivo. Our study provides the first direct evidence that chemerin undergoes extensive proteolytic processing in vivo, underlining the importance of measuring individual isoforms.
| Item Type: | Article |
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| Additional Information: | This manuscript contains data from work done at BWH/Harvard prior to my joining Novartis Archiving not formally supported |
| Keywords: | Carboxypeptidase; Chemokines; Immunology; Inflammation; Proteolytic enzymes ; arthritis; glioma; plasma |
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| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/5775 |