The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?
Version of Record online: 13 AUG 2004
Volume 113, Issue 1, pages 1–14, September 2004
How to Cite
Gregory, C. D. and Devitt, A. (2004), The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?. Immunology, 113: 1–14. doi: 10.1111/j.1365-2567.2004.01959.x
- Issue online: 13 AUG 2004
- Version of Record online: 13 AUG 2004
- Received 23 June 2004; accepted 8 July 2004
- cell interactions;
- inflammation: inflammatory mediators including eicosanoids;
Macrophages play important roles in the clearance of dying and dead cells. Typically, and perhaps simplistically, they are viewed as the professional phagocytes of apoptotic cells. Clearance by macrophages of cells undergoing apoptosis is a non-phlogistic phenomenon which is often associated with actively anti-inflammatory phagocyte responses. By contrast, macrophage responses to necrotic cells, including secondarily necrotic cells derived from uncleared apoptotic cells, are perceived as proinflammatory. Indeed, persistence of apoptotic cells as a result of defective apoptotic-cell clearance has been found to be associated with the pathogenesis of autoimmune disease. Here we review the mechanisms by which macrophages interact with, and respond to, apoptotic cells. We suggest that macrophages are especially important in clearing cells at sites of histologically visible, high-rate apoptosis and that, otherwise, apoptotic cells are removed largely by non-macrophage neighbours. We challenge the view that necrotic cells, including persistent apoptotic cells are, of necessity, proinflammatory and immunostimulatory and suggest that, under appropriate circumstances, persistent apoptotic cells can provide a prolonged anti-inflammatory stimulus.