Results of defective clearance of apoptotic cells: Lessons from knock-out mouse models

Abstract

The current stupefying array of molecules associated with the celearance of cells undergoing apoptosis not only demonstrates complexity in the process but also suggests redundancy. The molecular complexity is rooted in multiple cellular events, including (1) multiple stages in the apoptosis programme, (2) multiple steps in the processes that culminate in engulfment and (3) multiple responses of different phagocytes. While there is almost relentless discovery of molecules that are implicated in these events, studies of knock-out mice are beginning to reveal their biological significance. Here we review these investigations, which demonstrate that, in certain circumstances, defective apoptotic-cell clearance can be associated with the pathogenesis of autoimmune disease. However, these studies also show that persistence of apoptotic cells as a consequence of defective clearance is not, of necessity, pro-inflammatory and immunostimulatory. Indeed, it appears that, under appropriate circumstances, persistent apoptotic cells may provide prolonged anti-inflammatory signals. © 2009 Springer Netherlands.