Ficolin-2 recognizes DNA and participates in the clearance of dying host cells.
Ficolin-2 is a serum opsonin, which has been shown to be a pattern recognition molecule in the lectin complement activation pathway. Because innate immune mechanisms are involved in maintaining tissue homeostasis we hypothesized that Ficolin-2 also participate in the clearance of dying host cells. We found that Ficolin-2 binds to late apoptotic cells, as well as to apoptotic bodies and necrotic cells, but not to early apoptotic cells. We demonstrated that Ficolin-2 binds DNA in a calcium dependent manner and that DNA inhibits the binding to late apoptotic and necrotic cells, suggesting that DNA on permeable dying cells is a plausible ligand. Reconstituting serum deficient of Ficolin-2, C1q and mannose-binding lectin with Ficolin-2 augmented deposition of complement C4 on necrotic cells. Opsonization leads to an enhanced attachment/uptake of necrotic cells by macrophages. In conclusion dying host cells expose ligands with the capacity of binding Ficolin-2, which in turn leads to increased attachment and engulfment. Binding of Ficolin-2 to DNA points at nucleic acid exposed by permeable late apoptotic and necrotic cells as one of the ligands for Ficolin-2. Ficolin-2 may therefore be a scavenger molecule participating in the removal of host cells and maintenance of tissue homeostasis.
Jensen
Maria Lund
ML
Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark.
Honoré
Christian
C
Hummelshøj
Tina
T
Hansen
Bjarke Endel
BE
Madsen
Hans Ole
HO
Garred
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D016466:CHO Cells; D003167:Complement Activation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D037102:Lectins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009336:Necrosis / Q000276:immunology*; D009895:Opsonin Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D000097604:Ficolins
D000911:Antibodies, Monoclonal; D004247:DNA; D037102:Lectins; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D000097604:Ficolins