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

Andrew Devitt, Kate G. Parker, Carol Anne Ogden, Ceri Oldreive, Michael F. Clay, Lynsey A. Melville, Christopher O. Bellamy, Adam Lacy-Hulbert, Sophie C. Gangloff, Sanna M. Goyert, Christopher D. Gregory

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1161-1170
Number of pages10
JournalJournal of Cell Biology
Volume167
Issue number6
DOIs
Publication statusPublished - 20 Dec 2004

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Autoimmune Diseases
Inflammation
Macrophages
Anti-Inflammatory Agents
Phagocytosis
Autoantibodies

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Devitt, A., Parker, K. G., Ogden, C. A., Oldreive, C., Clay, M. F., Melville, L. A., ... Gregory, C. D. (2004). Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice. Journal of Cell Biology , 167(6), 1161-1170. https://doi.org/10.1083/jcb.200410057
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. ; Gregory, Christopher D. / Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice. In: Journal of Cell Biology . 2004 ; Vol. 167, No. 6. pp. 1161-1170.
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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.",
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Devitt, A, Parker, KG, Ogden, CA, Oldreive, C, Clay, MF, Melville, LA, Bellamy, CO, Lacy-Hulbert, A, Gangloff, SC, Goyert, SM & Gregory, CD 2004, 'Persistence of apoptotic cells without autoimmune disease or inflammation in CD14-/- mice', Journal of Cell Biology , vol. 167, no. 6, pp. 1161-1170. https://doi.org/10.1083/jcb.200410057

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.; Gregory, Christopher D.

In: Journal of Cell Biology , Vol. 167, No. 6, 20.12.2004, p. 1161-1170.

Research output: Contribution to journalArticle

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AU - Ogden, Carol Anne

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AU - Lacy-Hulbert, Adam

AU - Gangloff, Sophie C.

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AB - 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.

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