CXCL12 is displayed by rheumatoid endothelial cells through its basic amino-terminal motif on heparan sulfate proteoglycans

Arthritis Research & Therapy
B SantiagoJose Luis Pablos

Abstract

The chemokine CXCL12 (also known as stromal cell-derived factor, SDF-1) is constitutively expressed by stromal resident cells and is involved in the homeostatic and inflammatory traffic of leukocytes. Binding of CXCL12 to glycosaminoglycans on endothelial cells (ECs) is supposed to be relevant to the regulation of leukocyte diapedesis and neoangiogenesis during inflammatory responses. To improve our understanding of the relevance of this process to rheumatoid arthritis (RA), we have studied the mechanisms of presentation of exogenous CXCL12 by cultured RA ECs. RA synovial tissues had higher levels of CXCL12 on the endothelium than osteoarthritis (OA) tissues; in both, CXCL12 colocalized to heparan sulfate proteoglycans (HSPGs) and high endothelial venules. In cultured RA ECs, exogenous CXCL12alpha was able to bind in a CXCR4-independent manner to surface HSPGs. Desulfation of RA EC HSPGs by pretreatment with sodium chlorate, or by replacing in a synthetic CXCL12alpha the residues Lys24 and Lys27 by Ser (CXCL12alpha-K2427S), decreased or abrogated the ability of the chemokine to bind to RA ECs. Ex vivo, synovial ECs from patients with either OA or RA displayed a higher CXCL12-binding capacity than human umbilical vein ECs (HUVEC...Continue Reading

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Citations

Jan 16, 2007·Annals of the Rheumatic Diseases·Juan D CañeteJosé L Pablos
Oct 1, 2009·Arthritis Research & Therapy·Cem GabayBertrand Huard
Dec 29, 2009·Frontiers in Bioscience (Scholar Edition)·Zoltan SzekaneczAlisa E Koch
Mar 7, 2012·Immunologic Research·Miljana MomcilovićDjordje Miljković
Dec 7, 2011·The Biochemical Journal·Paramita RayGary D Luker
Feb 18, 2014·European Journal of Immunology·Ivan K H PoonMark D Hulett
Dec 13, 2006·International Journal of Cancer. Journal International Du Cancer·Behjatolah Monzavi-KarbassiThomas Kieber-Emmons
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Saloua ZrioualPierre Miossec
Apr 27, 2019·Frontiers in Immunology·Laleh KhodadadiFalk Hiepe
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Apr 17, 2020·Frontiers in Immunology·Helena CrijnsPaul Proost
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Mar 28, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhongwen ZhangXiaoqian Zhang

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Methods Mentioned

BETA
FCS
flow cytometry
transgenic

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