DOI: 10.1073/pnas.0334864100. Glycosaminoglycan binding and oligomerization are essential for the <i>in vivo</i> activity of certain chemokines

Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines

10.1073/pnas.0334864100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

During organogenesis, immunosurveillance, and inflammation, chemokines selectively recruit leukocytes by activating seven-transmembrane-spanning receptors. It has been suggested that an important component of this process is the formation of a haptotactic gradient by immobilization of chemokines on cell surface glycosaminoglycans (GAGs). However, this hypothesis has not been experimentally demonstrated in vivo . In the present study we investigated the effect of mutations in the GAG binding sites of three chemokines, monocyte chemoattractant protein-1/CC chemokine ligand (CCL)2, macrophage-inflammatory protein-1β/CCL4, and RANTES/CCL5, on their ability to recruit cells in vivo . These mutant chemokines retain chemotactic activity in vitro , but they are unable to recruit cells when administered intraperitoneally. Additionally, monomeric variants, although fully active in vitro , are devoid of activity in vivo . These data demonstrate that both GAG binding and the ability to form higher-order oligomers are essential for the activity of particular chemokines in vivo , although they are not required for receptor activation in vitro . Thus, quaternary structure of chemokines and their interaction with GAGs may significantly contribute to the localization of leukocytes beyond migration patterns defined by chemokine receptor interactions.

Bibliography

Proudfoot, A. E. I., Handel, T. M., Johnson, Z., Lau, E. K., LiWang, P., Clark-Lewis, I., Borlat, F., Wells, T. N. C., & Kosco-Vilbois, M. H. (2003). Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines. Proceedings of the National Academy of Sciences, 100(4), 1885â1890.

Authors 9

Amanda E. I. Proudfoot (first)
Tracy M. Handel (additional)
Zoë Johnson (additional)
Elaine K. Lau (additional)
Patricia LiWang (additional)
Ian Clark-Lewis (additional)
Frédéric Borlat (additional)
Timothy N. C. Wells (additional)
Marie H. Kosco-Vilbois (additional)

References 26 Referenced 647

10.1002/eji.1830230150
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10.1074/jbc.274.23.16077
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10.1021/bi9923196
A E Proudfoot, F Borlat Methods Mol Biol 138, 75–87 (2000). / Methods Mol Biol by Proudfoot A E (2000)
10.1021/bi991029m
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10.1021/bi000089l
10.1084/jem.179.3.881

Dates

Type	When
Created	22 years, 6 months ago (Feb. 18, 2003, 3:04 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 8:59 a.m.)
Indexed	1 week ago (Aug. 24, 2025, 6:58 p.m.)
Issued	22 years, 6 months ago (Feb. 5, 2003)
Published	22 years, 6 months ago (Feb. 5, 2003)
Published Online	22 years, 6 months ago (Feb. 5, 2003)
Published Print	22 years, 6 months ago (Feb. 18, 2003)

Funders 0

None

BibTeX

@article{Proudfoot_2003, title={Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0334864100}, DOI={10.1073/pnas.0334864100}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Proudfoot, Amanda E. I. and Handel, Tracy M. and Johnson, Zoë and Lau, Elaine K. and LiWang, Patricia and Clark-Lewis, Ian and Borlat, Frédéric and Wells, Timothy N. C. and Kosco-Vilbois, Marie H.}, year={2003}, month=feb, pages={1885–1890} }

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