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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1456-1465.)
© 1995 American Heart Association, Inc.

Articles

Interferon Gamma Binds to Extracellular Matrix Chondroitin-Sulfate Proteoglycans, Thus Enhancing Its Cellular Response

Eva Hurt Camejo; Birgitta Rosengren; Germán Camejo; Peter Sartipy; Gunnar Fager; Göran Bondjers

From the Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sahlgrenska University Hospital, and the Biochemistry Department Preclinical Research Laboratories (G.C.), Astra Hässle, Mölndal, Sweden.

Correspondence to Eva Hurt-Camejo, Wallenberg Laboratory, Sahlgrenska University Hospital, Göteborg University, Gothenburg S-41 345, Sweden. E-mail walevah@wlab.wall.gu.se.

Abstract The amino acid sequence of interferon gamma (IFN-) has basic amino acid clusters similar to the heparin-binding consensus sequences found in other proteins that bind to proteoglycans (PGs). We investigated whether recombinant human IFN- could bind to extracellular matrix (ECM) PGs secreted by human arterial smooth muscle cells (HASMCs) in vitro and whether the interaction affected the cellular response to IFN-. As an in vitro model of ECM we used the basement membrane from HASMCs in culture. The binding of ¹²⁵I-IFN- to ECM was reduced significantly by pretreatment of ECM with chondroitinase ABC, an enzyme that degrades chondroitin-sulfate glycosaminoglycans. IFN- binding to ECM was reduced by increasing concentrations of chondroitin-6-sulfate. ¹²⁵I-IFN- (0.05 to 2 ng/mL) binding data indicated an apparent K_d of 2x10^-11 mol/L and a maximum binding of 1.6x10⁶ IFN- molecules bound per square millimeter of ECM. Experiments with synthetic peptides suggested that residues 127 through 135 (AKTGKRKRS) are involved in the binding. The binding to chondroitin-sulfate PGs was confirmed by affinity chromatography of isolated [³⁵S]chondroitin-sulfate PGs from ECM and cell-culture medium on immobilized IFN-. The binding was abolished by treatment with chondroitinase ABC. ECM-bound IFN- was more effective in inducing the expression of class II major histocompatibility antigens such as HLA-DR in HASMCs and human arterial endothelial cells than soluble IFN-. These results suggest a role for chondroitin-sulfate PGs in immobilizing IFN- in the ECM compartment and enhancing the cellular response to IFN-.

Key Words: arteriosclerosis • interferon gamma • inflammation • proteoglycans

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