title: Syndecans, heparan sulfate proteoglycans, maintain the proteolytic balance of acute wound fluids.
abstract: An imbalance between proteases and antiproteases is thought to play a role in the inflammatory injury that regulates wound healing. The activities of some proteases and antiproteases found in inflammatory fluids can be modified in vitro by heparin, a mast cell-derived glycosaminoglycan. Because syndecans, a family of cell surface heparan sulfate proteoglycans, are the major cellular source of heparin-like glycosaminoglycan, we asked whether syndecans modify protease activities in vivo. Syndecan-1 and syndecan-4 ectodomains are shed into acute human dermal wound fluids (Subramanian, S. V., Fitzgerald, M. L., and Bernfield, M. (1997) J. Biol. Chem. 272, 14713-14720). Moreover, purified syndecan-1 ectodomain binds cathepsin G (Kd = 56 nM) and elastase (Kd = 35 nM) tightly and reduces the affinity of these proteases for their physiological inhibitors. Purified syndecan-1 ectodomain protects cathepsin G from inhibition by alpha1-antichymotrypsin and squamous cell carcinoma antigen 2 and elastase from inhibition by alpha1-proteinase inhibitor by decreasing second order rate constants for protease-antiprotease associations (kass) by 3700-, 32-, and 60-fold, respectively. Both enzymatic degradation of heparan sulfate and immunodepletion of the syndecan-1 and -4 in wound fluid reduce these proteolytic activities in the fluid, indicating that the proteases in the wound environment are regulated by interactions with syndecan ectodomains. Thus, syndecans are shed into acute wound fluids, where they can modify the proteolytic balance of the fluid. This suggests a novel physiological role for these soluble heparan sulfate proteoglycans.
authors.affiliation: Division of Developmental and Newborn Biology, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: V
authors.initials: V
authors.lastname: Kainulainen
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Schick
authors.forename: M
authors.initials: M
authors.lastname: Bernfield
mesh_terms: D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D010196:Pancreatic Elastase / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D012697:Serine Endopeptidases; D015843:Serpins / Q000378:metabolism; D012867:Skin / Q000201:enzymology; D012995:Solubility; D013552:Swine; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; C508304:SDC4 protein, human; C508242:Sdc1 protein, mouse; C508306:Sdc4 protein, mouse; D015843:Serpins; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; D004549:Elastin; D002403:Cathepsins; D010450:Endopeptidases; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; C534096:Ctsg protein, mouse; D010196:Pancreatic Elastase