Histidine-rich glycoprotein functions cooperatively with cell surface heparan sulfate on phagocytes to promote necrotic cell uptake.
Dying cells, such as apoptotic and necrotic cells, are cleared rapidly from the site of cell death to prevent the exposure of intracellular antigenic and immunostimulatory molecules that may cause tissue injury or facilitate the development of autoimmune diseases. For the immune system to recognize and remove dying cells efficiently, professional phagocytes use a variety of mechanisms that distinguish healthy cells from dying cells. HRG, a relatively abundant heparin/HS-binding protein in human plasma, has been shown recently to tether IgG specifically to necrotic cells and aid the phagocytic uptake of necrotic cells via a FcgammaRI-dependent pathway. In this study, we provide direct evidence that HRG can function cooperatively with cell surface HS on the monocytic cell line THP-1 to promote necrotic cell removal. In addition, we found that the presence of heparin can markedly inhibit HRG-enhanced necrotic cell clearance by THP-1 cells, possibly by blocking the ability of HRG to interact with necrotic cells as well as THP-1 cells. Thus, these data suggest that HRG can aid the phagocytosis of necrotic cells via a HS-dependent pathway, and this process can be regulated by the presence of certain HRG ligands, such as heparin.
Poon
Ivan K H
IK
Department of Immunology, The John Curtain School of Medical Research, Australian National University, Bldg. 131, Garran Rd., Acton, Canberra, ACT 0200 Australia.
Parish
Christopher R
CR
Hulett
Mark D
MD
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000378:metabolism; D003871:Dermatan Sulfate / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D018448:Models, Immunological; D009336:Necrosis / Q000276:immunology* / Q000473:pathology; D010586:Phagocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015032:Zinc / Q000494:pharmacology; D000099053:Histidine-Rich Glycoprotein
D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006427:Hemin; D006493:Heparin; D006497:Heparan Sulfate; D011506:Proteins; D015032:Zinc; D000099053:Histidine-Rich Glycoprotein