Syk is required for monocyte/macrophage chemotaxis to CX3CL1 (fractalkine)

Jean Claude Gevrey, Beth M. Isaac, Dianne Cox

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

CX3CL1 (fractalkine), the only member of the δ subclass of chemokines, is a known chemotactic factor for monocytes/macrophages as well as NK cells and T lymphocytes. In several pathologies, excessive production of CX3CL1 at specific sites leads primarily to monocyte/macrophage recruitment, which causes tissue and vascular damage. Despite their clinical relevance, the mechanisms underlying monocyte/macrophage chemotaxis to CX3CL1 remain poorly documented. The present report addresses this issue and identifies cell signaling crucial for this process. Using the murine monocyte/macrophage RAW cell line, we show that CX3CL1 treatment elicits a rapid and transient increase in F-actin and the formation of F-actin-enriched cell protrusions. CX3CL1 also triggers tyrosine phosphorylation of proteins localized in those protrusions. The protein tyrosine kinase Syk is activated upon CX3CL1 treatment, and reduction of Syk expression using RNA-mediated interference results in a specific and massive impairment of RAW cell migration to CX3CL1. Similar results are obtained using the Syk inhibitor, piceatannol. Cells with reduced Syk expression also exhibit a major defect in CX3CL1 -induced cytoskeletal remodeling. These data suggest that in monocytes/macrophages, Syk is essential for proper reorganization of the actin cytoskeleton in response to CX3CL1 and is therefore required for cell chemotaxis to CX3CL1.

Original languageEnglish (US)
Pages (from-to)3737-3745
Number of pages9
JournalJournal of Immunology
Volume175
Issue number6
StatePublished - Sep 15 2005

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Chemokine CX3CL1
Chemotaxis
Monocytes
Macrophages
Actins
Chemotactic Factors
RNA Interference
Actin Cytoskeleton
Chemokines
Natural Killer Cells
Protein-Tyrosine Kinases
Cell Movement
Blood Vessels
Tyrosine
Phosphorylation
Pathology
T-Lymphocytes
Cell Line
Therapeutics
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Syk is required for monocyte/macrophage chemotaxis to CX3CL1 (fractalkine). / Gevrey, Jean Claude; Isaac, Beth M.; Cox, Dianne.

In: Journal of Immunology, Vol. 175, No. 6, 15.09.2005, p. 3737-3745.

Research output: Contribution to journalArticle

Gevrey, Jean Claude ; Isaac, Beth M. ; Cox, Dianne. / Syk is required for monocyte/macrophage chemotaxis to CX3CL1 (fractalkine). In: Journal of Immunology. 2005 ; Vol. 175, No. 6. pp. 3737-3745.
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