The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells.
OBJECTIVE
Ficolin 3 (Hakata antigen), a collagen-like defense molecule, is a known autoantigen in patients with systemic lupus erythematosus (SLE). Recent studies have shown that other collagen-like defense molecules, such as C1q, mannose-binding lectin (MBL) and ficolin 2, bind to apoptotic cells and mediate their clearance by phagocytic cells. Dysfunction in this mechanism is regarded as an important contributor to the pathophysiology of SLE. Thus, we sought to determine whether ficolin 3 participates in the clearance of apoptotic cells.


METHODS
A Jurkat T cell line was used as the source of dying host cells. The cells were rendered apoptotic or necrotic by incubation with etoposide or by heat shocking, respectively. Binding of ficolin 3 to the cells was analyzed by flow cytometry. The apoptotic cells were incubated with human monocyte-derived macrophages, and the effect of ficolin 3 on the adhesion/uptake was examined by flow cytometry.


RESULTS
Ficolin 3 bound to a population of late apoptotic cells, while a strong and uniform binding to necrotic cells was observed. The binding properties differed from those of MBL and ficolin 2. Ficolin 3 binding to late apoptotic cells resulted in a significant increase in adhesion/uptake by macrophages.


CONCLUSIONS
Ficolin 3 mediates the clearance of late apoptotic cells, which suggests that this protein is involved in the maintenance of tissue homeostasis and might play a protective role against the development of autoimmunity.
Honoré
Christian
C
Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Hummelshoj
Tina
T
Hansen
Bjarke E
BE
Madsen
Hans O
HO
Eggleton
Paul
P
Garred
Peter
P
D017209:Apoptosis / Q000502:physiology*; D015551:Autoimmunity / Q000502:physiology; D002118:Calcium / Q000502:physiology; D037282:Calreticulin / Q000378:metabolism; D002478:Cells, Cultured; D006023:Glycoproteins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D019169:Jurkat Cells; D037102:Lectins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D010587:Phagocytosis / Q000502:physiology; D011485:Protein Binding
D037282:Calreticulin; C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins; D002118:Calcium