- Paper Report
- Open Access
Versican modulates cellular responses
- Alaina J Ammit1
© Biomed Central Ltd 2001
- Received: 8 March 2001
- Accepted: 18 September 2001
- Published: 18 September 2001
- Chemokines, ECM, proteoglycans, versican
Proteoglycans are proteins with covalently linked glycosaminoglycans (GAGs). Because GAGs such as heparan sulfate (HS) and chondroitin sulfate (CS) are negatively charged, proteoglycans are able to bind many positively charged molecules, including chemokines. Recently, HS proteoglycans have been shown to promote presentation of chemokines to their specific receptors and to potentiate cellular signalling. CS proteoglycans may also have this function. The aim of this study was to examine the ability of versican, a CS proteoglycan secreted into the extracellular matrix (ECM) by a variety of cells, to bind a large panel of chemokines and the biological consequences of such binding.
Versican binds a variety of chemokines, including (amongst others) secondary lymphoid tissue chemokine (SLC). GAG-degrading enzymes (chrondroitinases) attentuate binding of SLC to versican, thus confirming that versican binds chemokines in a GAG-dependent manner. Rather than potentiating chemokine-induced responses, versican downregulates the integrin-mediated cell adhesion induced by SLC as well as chemokine-induced intracellular Ca2+ mobilization. The authors conclude that versican binds specific chemokines through its CS chains but that the binding tends to downregulate chemokine function. The inhibitory mechanism remains unclear, versican allows SLC to bind its receptor even after forming a complex with SLC, but inhibits transduction of an appropriate signal.
Dot blot analysis, ELISA, cell adhesion assay, Ca2+ mobilization assay, radioligand binding assay
Roberts CR: Is asthma a fibrotic disease? Chest 1995, 107:111S-117S.
Huang J, Olivenstein R, Taha R, Hamid Q, Ludwig M: Enhanced proteoglycan deposition in the airway wall of atopic asthmatics. Am J Respir Crit Care Med 1999, 160:725-729.
Johnson PRA, Black JL, Carlin S, Ge Q, Underwood PA: The production of extracellular matrix proteins by human passively sensitized airway smooth-muscle cells in culture: the effects of beclomethasome. Am J Respir Crit Care Med 2000, 162:2145-2151.
Zhang Y, Cao L, Kiani C, Yang BL, Hu W, Yang BB: Promotion of chondrocyte proliferation by versican mediated by G1 domain and EGF-like motifs. J Cell Biochem 1999, 73:445-457.