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The Journal of Immunology, 2002, 169: 4745-4751.
Copyright © 2002 by The American Association of Immunologists

Histidine-Rich Glycoprotein Binds to DNA and Fc{gamma}RI and Potentiates the Ingestion of Apoptotic Cells by Macrophages1

Nick N. Gorgani, Brian A. Smith, Dwight H. Kono and Argyrios N. Theofilopoulos2

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{gamma}RI mAb inhibited HRG binding to HMDM, while DNA, but not chromatin, inhibited HRG binding to apoptotic cells, and either anti-Fc{gamma}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{gamma}RI on HMDM, is a key physiological mediator of apoptotic cell clearance by macrophages.




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