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

Devitt, Andrew, Parker, Kate G., Ogden, Carol Anne, Oldreive, Ceri, Clay, Michael F., Melville, Lynsey A., Bellamy, Christopher O., Lacy-Hulbert, Adam, Gangloff, Sophie C., Goyert, Sanna M. and Gregory, Christopher D. (2004). Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice. Journal of Cell Biology, 167 (6), pp. 1161-1170.

Abstract

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.

Publication DOI: https://doi.org/10.1083/jcb.200410057
Divisions: Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Pharmacy
Additional Information: Creative Commons Attribution Non-Commercial License
Full Text Link:
Related URLs: http://jcb.rupr ... tent/167/6/1161 (Publisher URL)
Published Date: 2004-12-20
Authors: Devitt, Andrew ( 0000-0002-4651-6761)
Parker, Kate G.
Ogden, Carol Anne
Oldreive, Ceri
Clay, Michael F.
Melville, Lynsey A.
Bellamy, Christopher O.
Lacy-Hulbert, Adam
Gangloff, Sophie C.
Goyert, Sanna M.
Gregory, Christopher D.

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