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Published 20 December 2004. doi:10.1083/jcb.200410057
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 6, 1161-1170
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Article

Persistence of apoptotic cells without autoimmune disease or inflammation in CD14–/– mice



Andrew Devitt1, Kate G. Parker3, Carol Anne Ogden1, Ceri Oldreive1, Michael F. Clay1, Lynsey A. Melville1, Christopher O. Bellamy2, Adam Lacy-Hulbert1, Sophie C. Gangloff4, Sanna M. Goyert4, and Christopher D. Gregory1

1 Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH8 9XD, Scotland, UK
2 Department of Pathology, University of Edinburgh, Edinburgh, EH8 9XD, Scotland, UK
3 School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, England, UK
4 North Shore University Hospital, Manhasset, NY 11030

Correspondence to C. Gregory: chris.gregory{at}ed.ac.uk

Interaction of macrophages with apoptotic cells involves multiple steps including recognition, tethering, phagocytosis, and anti-inflammatory macrophage responses. Defective apoptotic cell clearance is associated with pathogenesis of autoimmune disease. CD14 is a surface receptor that functions in vitro in the removal of apoptotic cells by human and murine macrophages, but its mechanism of action has not been defined. Here, we demonstrate that CD14 functions as a macrophage tethering receptor for apoptotic cells. Significantly, CD14–/– macrophages in vivo are defective in clearing apoptotic cells in multiple tissues, suggesting a broad role for CD14 in the clearance process. However, the resultant persistence of apoptotic cells does not lead to inflammation or increased autoantibody production, most likely because, as we show, CD14–/– macrophages retain the ability to generate anti-inflammatory signals in response to apoptotic cells. We conclude that CD14 plays a broad tethering role in apoptotic cell clearance in vivo and that apoptotic cells can persist in the absence of proinflammatory consequences.

S.C. Gangloff's present address is University of Reims Champagne Ardenne, EA2070 -IFR53, 51 100 Reims, France.

Abbreviations used in this paper: ACAMP, apoptotic cell–associated molecular pattern; ANA, anti-nuclear antibodies; AxV, annexin V; BL, Burkitt lymphoma; BMDM, bone marrow–derived macrophage; HMDM, human monocyte-derived macrophage; ISEL, in situ end labelling; PAMP, pathogen-associated molecular pattern; PI, propidium iodide; PRR, pattern recognition receptor; PS, phosphatidylserine.


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