The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis.
Apoptotic cells must be rapidly eliminated to avoid harmful inflammatory and autoimmune reactions. Innate immunity is designed/poised to identify dying cells by their unique surface-associated molecular patterns. Here we demonstrate for the first time, to our knowledge, that the human complement protein properdin binds to early apoptotic T cells and initiates complement activation, leading to C3b opsonization and ingestion by phagocytic cells. Properdin binding was facilitated by the glycosaminoglycan chains of surface proteoglycans. Properdin released by activated neutrophils was particularly effective at recognition of apoptotic T cells, whereas the binding activity of properdin in the serum appeared to be inhibited. "Properdin tagging" of apoptotic T cells also induced their uptake by phagocytes independent of complement activation or other complement proteins. Although our findings were made primarily with apoptotic T cells, they suggest that properdin could play a similar role during apoptosis of other cell types.
Kemper
Claudia
C
Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mitchell
Lynne M
LM
Zhang
Lijuan
L
Hourcade
Dennis E
DE
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000473:pathology; D003167:Complement Activation / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006025:Glycosaminoglycans / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000166:cytology / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D011414:Properdin / Q000276:immunology*; D011485:Protein Binding; D011509:Proteoglycans / Q000276:immunology
D006025:Glycosaminoglycans; D011509:Proteoglycans; D011414:Properdin; D003179:Complement C3b