The macrophage and the apoptotic cell: an innate immune interaction viewed simplistically?

Christopher D. Gregory, Andrew Devitt

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1-14
Number of pages14
Issue number1
Early online date13 Aug 2004
Publication statusPublished - Sept 2004


  • apoptosis
  • cell interactions
  • inflammation
  • inflammatory mediators including eicosanoids
  • macrophages
  • monocytes
  • phagocytosis


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