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J Biol Chem, Vol. 275, Issue 8, 5987-5996, February 25, 2000
From the Apoptosis is a physiological program for the
deletion of cells in which caspases govern events leading to safe
clearance by phagocytes. However, a growing weight of evidence now
suggests that not all forms of programmed cell death are
caspase-dependent. We now report a complete and
constitutive but caspase-independent program for the specific
phagocytic clearance of intact effete platelets, anucleated blood cells
of critical importance in health and disease. Platelets aged in
vitro not only exhibited increased expression of proapoptotic Bak
and Bax but also evidenced constitutive diminution of function such as
decreased aggregation to ADP, which was accelerated by culture in the
absence of plasma. This abrogation of cell function in plasma-deprived
platelets was associated with morphological and biochemical features
similar to those of granulocyte apoptosis, that is, cytoplasmic
condensation, plasma membrane changes including exposure of
phosphatidylserine and the granule protein P-selectin, and recognition
by phagocyte scavenger receptors. However, and in contrast with
constitutive death of other inflammatory blood cells by apoptosis,
these events were not affected by caspase inhibitors, nor was there
evidence of caspase-3 activation either by hydrolysis of analog peptide
substrates or Western blot analysis, serving to emphasize that neither
programmed cell death nor clearance by phagocytes need involve caspases.
Constitutive Death of Platelets Leading to Scavenger
Receptor-mediated Phagocytosis
A CASPASE-INDEPENDENT CELL CLEARANCE PROGRAM*
§¶,§,
,
Centre for Inflammation Research, Department
of Clinical & Surgical Sciences (Internal Medicine), Royal
Infirmary, Edinburgh, EH3 9YW and the Divisions of Renal & Inflammatory Disease and ** Cardiovascular Medicine, Department of
Medicine, University Hospital,
Nottingham NG7 2UH, United Kingdom
*
This work was supported in part by Wellcome Trust Program
Grant 047273 (to J. S.) and a National Kidney Research Foundation studentship (to M. C. H. C.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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