NDLI: Chemokine cooperativity is caused by competitive glycosaminoglycan binding

Content Provider	PubMed Central
Author	Folkert, Verkaar Van, Offenbeek Jody Lee, Miranda M. C. Van Der Lith, Lambertus H. C. J. Van Watts, Anne O. Rops, Angelique L. W. M. M. Aguilar, David C. Ziarek, Joshua J. Vlag, Johan Van Der Handel, Tracy M. Volkman, Brian F. Proudfoot, Amanda E. I. Vischer, Henry F. Zaman, Guido J. R. Smit, Martine J.
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”. Here, 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, where multiple chemokines are secreted simultaneously.
Related Links	http://dx.doi.org/10.4049/jimmunol.1302159
Ending Page	3914
Page Count	7
Starting Page	3908
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	8
Volume Number	192
Language	English
Publisher Date	2014-04-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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