A cellulose-binding domain-fused recombinant human T cell connective tissue-activating peptide-III manifests heparanase activity

The chemokine connective tissue-activating peptide (CTAP)-III, which belong s to the leukocyte-derived growth factor family of mediators, was previousl y shown to be mitogenic for fibroblasts. However, it has recently been show n that CTAP-III, released from platelets, can act like a heparanase enzyme and degrade heparan sulfate. This suggests that CTAP-III may also function as a proinflammatory mediator. We have successfully cloned CTAP-III from a lambda gt11 cDNA library of PHA-activated human CD4(+) T cells and produced recombinant CTAP-III as a fusion protein with a cellulose-binding domain m oiety. This recombinant CTAP-III exhibited heparanase activity and released degradation products from metabolically labeled, naturally produced extrac ellular matrix. We have also developed polyclonal and monoclonal antibodies , and these antibodies against the recombinant CTAP-III detected the CTAP-I II molecule in human T cells, polymorphonuclear leukocytes, and placental e xtracts. Thus, our study provides tools to examine further immune cell beha vior in inflamed sites rich with extracellular moieties and proinflammatory mediators. (C) 1999 Academic Press.