Journal
BLOOD
Volume 112, Issue 13, Pages 5026-5036Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-06-162404
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Funding
- Leukemia Research (London, United Kingdom)
- Medical Research Council (London, United Kingdom)
- Medical Research Council [G9900991B] Funding Source: researchfish
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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. (Blood. 2008; 112: 5026-5036)
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