Submitted June 10, 2008
Accepted August 18, 2008
CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis
Lucy A. Truman, Catriona A. Ford, Marta Pasikowska, John D. Pound, Sarah J. Wilkinson, Ingrid E. Dumitriu, Lynsey Melville, Lauren A. Melrose, Carol Anne Ogden, Robert Nibbs, Gerard Graham, Christophe Combadiere, and Christopher D. Gregory*
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, Lothian, United Kingdom
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, Lanarkshire, United Kingdom
INSERM U543, Laboratoire d'Immunologie Cellulaire, Faculte de Medecine Pitie-Salpetiere, Paris, France
* Corresponding author; email: chris.gregory{at}ed.ac.uk.
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 CX3 CL1/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 upon macrophage fractalkine receptor, CX3CR1. CX 3CR1-deficiency caused diminished recruitment of macrophages to germinal centres 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.
