Direct macrophage recognition of an externalized phosphatidylserine signal
on senescent erythrocytes is a process of erythrophagocytic clearance that
is in line with the general clearance process of all other circulating cell
s that become apoptotic, Advances in deciphering this process suggest that
oxidation of the erythrocyte's hemoglobin, the salient target of the free r
adicals encountered in the circulatory environment, may drive subsequent st
eps. The progressive accumulation of oxidized hemoglobin covalently bound t
o the membrane skeleton not only disrupts membrane organization but also th
reatens eventual phospholipid oxidation via a calcium-promoted quasi-lipoxy
genase activity. The emergence on the cell surface of a threshold concentra
tion of oxidized phospholipids, principally phosphatidylserine, signals rec
ognition by the CD36 macrophage receptor. (C) 2000 Lippincott Williams & Wi
lkins, Inc.