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Chemokine cooperativity is caused by competitive glycosaminoglycan binding. J Immunol 2014 Apr 15;192(8):3908-3914

Date

03/19/2014

Pubmed ID

24639348

Pubmed Central ID

PMC4198333

DOI

10.4049/jimmunol.1302159

Scopus ID

2-s2.0-84898636375   14 Citations

Abstract

Chemokines comprise a family of secreted proteins that activate G protein-coupled chemokine receptors and thereby control the migration of leukocytes during inflammation or immune surveillance. The positional information required for such migratory behavior is governed by the binding of chemokines to membrane-tethered glycosaminoglycans (GAGs), which establishes a chemokine concentration gradient. An often observed but incompletely understood behavior of chemokines is the ability of unrelated chemokines to enhance the potency with which another chemokine subtype can activate its cognate receptor. This phenomenon has been demonstrated to occur between many chemokine combinations and across several model systems and has been dubbed chemokine cooperativity. In this study, we have used GAG binding-deficient chemokine mutants and cell-based functional (migration) assays to demonstrate that chemokine cooperativity is caused by competitive binding of chemokines to GAGs. This mechanistic explanation of chemokine cooperativity provides insight into chemokine gradient formation in the context of inflammation, in which multiple chemokines are secreted simultaneously.

Author List

Verkaar F, van Offenbeek J, van der Lee MMC, van Lith LHCJ, Watts AO, Rops ALWMM, Aguilar DC, Ziarek JJ, van der Vlag J, Handel TM, Volkman BF, Proudfoot AEI, Vischer HF, Zaman GJR, Smit MJ

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Binding, Competitive
CHO Cells
Chemokine CCL19
Chemokine CCL21
Chemokine CXCL13
Chemokines
Chemotaxis
Cricetinae
Cricetulus
Glycosaminoglycans
Models, Biological
Protein Binding
Protein Multimerization
Receptors, Chemokine
jenkins-FCD Prod-444 eb4ebd1a08581aba961d3befd3b851a3c3ec6b46