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Vol. 12, Issue 4, 919-930, April 2001
Department of Microbiology and Immunology, University of Illinois
College of Medicine, Chicago, Illinois 60612
The distinction between physiological (apoptotic) and pathological
(necrotic) cell deaths reflects mechanistic differences in cellular
disintegration and is of functional significance with respect to the
outcomes that are triggered by the cell corpses. Mechanistically,
apoptotic cells die via an active and ordered pathway; necrotic deaths,
conversely, are chaotic and passive. Macrophages and other phagocytic
cells recognize and engulf these dead cells. This clearance is believed
to reveal an innate immunity, associated with inflammation in cases of
pathological but not physiological cell deaths. Using objective and
quantitative measures to assess these processes, we find that
macrophages bind and engulf native apoptotic and necrotic cells to
similar extents and with similar kinetics. However, recognition of
these two classes of dying cells occurs via distinct and noncompeting
mechanisms. Phosphatidylserine, which is externalized on both apoptotic
and necrotic cells, is not a specific ligand for the recognition of
either one. The distinct modes of recognition for these different
corpses are linked to opposing responses from engulfing macrophages.
Necrotic cells, when recognized, enhance proinflammatory responses of
activated macrophages, although they are not sufficient to trigger
macrophage activation. In marked contrast, apoptotic cells profoundly
inhibit phlogistic macrophage responses; this represents a
cell-associated, dominant-acting anti-inflammatory signaling activity
acquired posttranslationally during the process of physiological cell death.
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