Histidine-rich glycoprotein binds to DNA and Fc gamma RI and potentiates the ingestion of apoptotic cells by macrophages.
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-FcgammaRI mAb inhibited HRG binding to HMDM, while DNA, but not chromatin, inhibited HRG binding to apoptotic cells, and either anti-FcgammaRI or DNA abrogated the HRG-dependent ingestion. The findings indicate that HRG, by acting as a bridge between DNA on apoptotic cells and FcgammaRI on HMDM, is a key physiological mediator of apoptotic cell clearance by macrophages.
Gorgani
Nick N
NN
Department of Immunology/IMM3, The Scripps Research Institute, La Jolla, CA 92037, USA.
Smith
Brian A
BA
Kono
Dwight H
DH
Theofilopoulos
Argyrios N
AN
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D015922:Complement C1q / Q000502:physiology; D004247:DNA / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D006639:Histidine / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D017452:Receptors, IgG / Q000378:metabolism* / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019699:Thrombospondins / Q000097:blood / Q000502:physiology; D014407:Tumor Cells, Cultured; D000099053:Histidine-Rich Glycoprotein
D000276:Adjuvants, Immunologic; D004268:DNA-Binding Proteins; D011506:Proteins; D017452:Receptors, IgG; D019699:Thrombospondins; D000099053:Histidine-Rich Glycoprotein; D006639:Histidine; D015922:Complement C1q; D004247:DNA