Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement.
BACKGROUND
Defects in phagocytosis of apoptotic cells have a role in the pathogenesis of autoimmune diseases. Decrease of phagocytosis of apoptotic cells occurs in systemic lupus erythematosus (SLE). Factors underlying this decrease are, presently, unknown.


OBJECTIVE
To analyse the expression of relevant membrane receptors of monocyte derived macrophages (MDM) from patients with SLE and assess their ability to phagocytose apoptotic cells in comparison with MDM from healthy controls. Additionally, to compare phagocytosis in the presence of SLE sera with that in normal human serum (NHS).


METHODS
Human peripheral blood monocytes were isolated from patients and controls, and cultured for 7 days to obtain MDM. Membrane expression of CD14, CD18, CD36, and CD51/61 was measured. MDM were incubated with apoptotic Jurkat cells in the presence of NHS or serum from patients with active or inactive disease.


RESULTS
No differences in phagocytosis capacity were found between MDM from patients and controls. Membrane expression of the respective receptors was comparable in patients and controls. However, when MDM from controls were incubated with apoptotic cells in patient serum, phagocytosis was significantly decreased in comparison with incubation in NHS. This effect depended on the patients' disease activity and could be reversed by addition of NHS. Reduced uptake of apoptotic cells was associated with decreased levels of complement C1q, C4, and C3, but not with levels of complement factor B.


CONCLUSIONS
Reduced uptake of apoptotic cells by MDM from patients with SLE is not an intrinsic defect but is serum dependent and associated with decreased levels of C1q, C4, and C3.
Bijl
M
M
Department of Internal Medicine, Division of Clinical Immunology, University Hospital, The Netherlands. m.bijl@int.azg.nl
Reefman
E
E
Horst
G
G
Limburg
P C
PC
Kallenberg
C G M
CG
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000172:deficiency; D003176:Complement C3 / Q000172:deficiency; D003181:Complement C4 / Q000172:deficiency; D003165:Complement System Proteins / Q000172:deficiency*; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000378:metabolism; D012720:Severity of Illness Index
D003176:Complement C3; D003181:Complement C4; D011971:Receptors, Immunologic; D015922:Complement C1q; D003165:Complement System Proteins