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 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.
Truman
Lucy A
LA
Medical Research Council (MRC) Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom.
Ford
Catriona A
CA
Pasikowska
Marta
M
Pound
John D
JD
Wilkinson
Sarah J
SJ
Dumitriu
Ingrid E
IE
Melville
Lynsey
L
Melrose
Lauren A
LA
Ogden
Carol Anne
CA
Nibbs
Robert
R
Graham
Gerard
G
Combadiere
Christophe
C
Gregory
Christopher D
CD
D000818:Animals; D017209:Apoptosis; D002051:Burkitt Lymphoma; D020169:Caspases; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D002633:Chemotaxis; D006801:Humans; D008198:Lymph Nodes; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2
D054428:Chemokine CX3CL1; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases