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RI and Potentiates the Ingestion of Apoptotic Cells by Macrophages1
Department of Immunology/IMM3, The Scripps Research Institute, La Jolla, CA 92037
Histidine-rich glycoprotein (HRG) is an abundant serum protein that
exhibits many functions in diverse biological systems. In this study,
we show that HRG potentiates the ingestion of apoptotic cells by mature
human monocyte-derived macrophages (HMDM). HRG bound specifically to
apoptotic Jurkat cells and mature HMDM in a saturable and
concentration-dependent manner. Purified HRG or HRG in sera increased
the number of HMDM-containing apoptotic cells and accelerated the
ingestion, while neutralization or depletion of HRG from sera reduced
this effect. Anti-Fc
RI mAb inhibited HRG binding to HMDM, while DNA,
but not chromatin, inhibited HRG binding to apoptotic cells, and either
anti-Fc
RI or DNA abrogated the HRG-dependent ingestion. The
findings indicate that HRG, by acting as a bridge between DNA on
apoptotic cells and Fc
RI on HMDM, is a key physiological mediator of
apoptotic cell clearance by macrophages.
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