Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte migration via inhibition of stress-activated protein kinase 2/p38 and matrix metalloproteinase activities

Sébastien Vitale; Annie Schmid-Alliana; Véronique Breuil; Manuel Pomeranz; Marie-Ange Millet; Bernard Rossi; Heidy Schmid-Antomarchi

doi:10.4049/jimmunol.172.1.585

Soluble fractalkine prevents monocyte chemoattractant protein-1-induced monocyte migration via inhibition of stress-activated protein kinase 2/p38 and matrix metalloproteinase activities

J Immunol. 2004 Jan 1;172(1):585-92. doi: 10.4049/jimmunol.172.1.585.

Authors

Sébastien Vitale¹, Annie Schmid-Alliana, Véronique Breuil, Manuel Pomeranz, Marie-Ange Millet, Bernard Rossi, Heidy Schmid-Antomarchi

Affiliation

¹ Institut National de la Santé et de la Recherche Médicale, Unité 364, Institut Féderatif de Recherche 50, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 02, France.

PMID: 14688370
DOI: 10.4049/jimmunol.172.1.585

Abstract

In this study, we address the question of the cross-talk between two chemokines that are cosecreted during inflammation, namely monocyte chemoattractant protein-1 (MCP-1) and soluble fractalkine (s-FKN), toward monocyte migration. We found that s-FKN fails to induce MonoMac6 cell migration per se. Interestingly, this chemokine antagonizes transendothelial migration and chemotaxis of MonoMac6 cells and freshly isolated human monocytes induced by MCP-1, indicating a direct effect of s-FKN on monocytic cells. In this study, we found that stress-activated protein kinase (SAPK)1/c-Jun N-terminal kinase 1 and SAPK2/p38 are involved in the control of MCP-1-induced MonoMac6 cell migration. We demonstrated that s-FKN abrogates the MCP-1-induced SAPK2/p38 activation as well as the upstream Pyk2 activity. Furthermore, we observed that s-FKN also inhibits the activity of a major matrix metalloproteinase (MMP), namely MMP-2. Taken collectively, our results indicate that the s-FKN antagonizes the chemoattractant effect of MCP-1 on monocytes, likely by inhibiting crucial signaling pathways, like SAPK2/p38 and MMP-2 activities.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line
Cell Line, Tumor
Cell Migration Inhibition*
Cell Separation
Chemokine CCL2 / antagonists & inhibitors
Chemokine CCL2 / physiology*
Chemokine CX3CL1
Chemokines, CX3C / physiology*
Chemotaxis, Leukocyte / immunology*
Endothelium, Vascular / cytology
Endothelium, Vascular / immunology
Enzyme Activation / immunology
Enzyme Induction / immunology
Enzyme Inhibitors / pharmacology
Focal Adhesion Kinase 2
Humans
Matrix Metalloproteinase 2 / biosynthesis
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 2 / physiology
Matrix Metalloproteinase Inhibitors*
Membrane Proteins / physiology*
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Mitogen-Activated Protein Kinases / biosynthesis
Mitogen-Activated Protein Kinases / metabolism
Mitogen-Activated Protein Kinases / physiology
Monocytes / cytology
Monocytes / enzymology*
Monocytes / immunology
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / biosynthesis
Protein-Tyrosine Kinases / metabolism
Solubility
p38 Mitogen-Activated Protein Kinases

Substances

CX3CL1 protein, human
Chemokine CCL2
Chemokine CX3CL1
Chemokines, CX3C
Enzyme Inhibitors
Matrix Metalloproteinase Inhibitors
Membrane Proteins
Protein-Tyrosine Kinases
Focal Adhesion Kinase 2
Mitogen-Activated Protein Kinases
p38 Mitogen-Activated Protein Kinases
Matrix Metalloproteinase 2