CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis

Cells undergoing apoptosis are efficiently located and engulfed by phagocytes. The mechanisms by which macrophages, the professional scavenging phagocytes of apoptotic cells, are attracted to sites of apoptosis are poorly defined. Here we show that CX3CL1/fractalkine, a chemokine and intercellular a...

Full description

Saved in:
Bibliographic Details
Published in:Blood 2008-12, Vol.112 (13), p.5026-5036
Main Authors: Truman, Lucy A., Ford, Catriona A., Pasikowska, Marta, Pound, John D., Wilkinson, Sarah J., Dumitriu, Ingrid E., Melville, Lynsey, Melrose, Lauren A., Ogden, Carol Anne, Nibbs, Robert, Graham, Gerard, Combadiere, Christophe, Gregory, Christopher D.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biological and medical sciences
Burkitt Lymphoma
Caspases
Cell Line, Tumor
Cells, Cultured
Chemokine CX3CL1 - metabolism
Chemotaxis
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunobiology
Lymph Nodes
Lymphocytes - cytology
Lymphocytes - metabolism
Macrophages - physiology
Mice
Mice, Inbred BALB C
Monocytes, macrophages
Myeloid cells: ontogeny, maturation, markers, receptors
Proto-Oncogene Proteins c-bcl-2
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cells undergoing apoptosis are efficiently located and engulfed by phagocytes. The mechanisms by which macrophages, the professional scavenging phagocytes of apoptotic cells, are attracted to sites of apoptosis are poorly defined. Here we show that CX3CL1/fractalkine, a chemokine and intercellular adhesion molecule, is released rapidly from apoptotic lymphocytes, via caspase- and Bcl-2-regulated mechanisms, to attract macrophages. Effective chemotaxis of macrophages to apoptotic lymphocytes is dependent on macrophage fractalkine receptor, CX3CR1. CX3CR1 deficiency caused diminished recruitment of macrophages to germinal centers of lymphoid follicles, sites of high-rate B-cell apoptosis. These results provide the first demonstration of chemokine/chemokine-receptor activity in the navigation of macrophages toward apoptotic cells and identify a mechanism by which macrophage infiltration of tissues containing apoptotic lymphocytes is achieved.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-06-162404