title: Effect of posttranslational processing on the in vitro and in vivo activity of chemokines.
abstract: The CXC and CC chemokine gene clusters provide an abundant number of chemotactic factors selectively binding to shared G protein-coupled receptors (GPCR). Hence, chemokines function in a complex network to mediate migration of the various leukocyte subsets, expressing specific GPCRs during the immune response. Further fine-tuning of the chemokine system is reached through specific posttranslational modifications of the mature proteins. Indeed, enzymatic processing of chemokines during an early phase of inflammation leads to activation of precursor molecules or cleavage into even more active or receptor specific chemokine isoforms. At a further stage, proteolytic processing leads to loss of GPCR signaling, thereby providing natural chemokine receptor antagonists. Finally, further NH(2)-terminal cleavage results in complete inactivation to dampen the inflammatory response. During inflammatory responses, the two chemokines which exist in a membrane-bound form may be released by proteases from the cellular surface. In addition to proteolytic processing, citrullination and glycosylation of chemokines is also important for their biological activity. In particular, citrullination of arginine residues seems to reduce the inflammatory activity of chemokines in vivo. This goes along with other positive and negative regulatory mechanisms for leukocyte migration, such as chemokine synergy and scavenging by decoy receptors.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. anneleen.mortier@rega.kuleuven.be
authors.forename: Anneleen
authors.initials: A
authors.lastname: Mortier
authors.forename: Mieke
authors.initials: M
authors.lastname: Gouwy
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
mesh_terms: D000818:Animals; D018925:Chemokines / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction / Q000276:immunology
chemical_list: D018925:Chemokines