By the same authors

From the same journal

From the same journal

CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration

Research output: Contribution to journalArticle

Full text download(s)

Author(s)

  • James Martin Fox
  • Fahima Kausar
  • Amy Day
  • Michael Osborne
  • Khansa Hussain
  • Anja Mueller
  • Jessica Lin
  • Tomoko Tsuchiya
  • Shiro Kanegasaki
  • James Pease

Department/unit(s)

Publication details

JournalScientific Reports
DateAccepted/In press - 5 Jun 2018
DatePublished (current) - 21 Jun 2018
Issue number1
Volume8
Number of pages15
Original languageEnglish

Abstract

Activated platelets release micromolar concentrations of the chemokine CXCL4/Platelet Factor-4. Deposition of CXCL4 onto the vascular endothelium is involved in atherosclerosis, facilitating monocyte arrest and recruitment by an as yet, unidentified receptor. Here, we demonstrate that CXCL4 drives chemotaxis of the monocytic cell line THP-1. Migration and intracellular calcium responses induced by CXCL4 were pertussis toxin-sensitive, implicating a GPCR in signal transduction. Cell treatment with chondroitinase ABC ablated migration, suggesting that cis presentation of CXCL4 by cell surface glycosaminoglycans to a GPCR is required. Although CXCR3 has been previously described as a CXCL4 receptor, THP-1 cells were unresponsive to CXCR3 ligands and CXCL4-induced migration was insensitive to a CXCR3 antagonist, suggesting that an alternative receptor is involved. Interrogating CC-class chemokine receptor transfectants, we unexpectedly found that CXCL4 could induce the migration of CCR1-expressing cells and also induce CCR1 endocytosis. Extending our findings to primary human monocytes, we observed that CXCL4 induced CCR1 endocytosis and could induce monocyte chemotaxis in a CCR1 antagonist-sensitive manner. Collectively, our data identify CCR1 as a previously elusive monocyte CXCL4 receptor and suggest that CCR1 may play a role in inflammation where the release of CXCL4 is implicated.

Bibliographical note

© The Author(s), 2018.

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations