Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement

被引:120
作者
Bijl, M
Reefman, E
Horst, G
Limburg, PC
Kallenberg, CGM
机构
[1] Univ Groningen Hosp, Div Clin Immunol, Dept Internal Med, NL-9700 RB Groningen, Netherlands
[2] Univ Groningen Hosp, Dept Pathol & Lab Med, NL-9700 RB Groningen, Netherlands
关键词
D O I
10.1136/ard.2005.035733
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:57 / 63
页数:7
相关论文
共 50 条
  • [1] Mechanisms of phagocytosis in macrophages
    Aderem, A
    Underhill, DM
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 : 593 - 623
  • [2] Baumann I, 2002, ARTHRITIS RHEUM-US, V46, P191, DOI 10.1002/1529-0131(200201)46:1<191::AID-ART10027>3.0.CO
  • [3] 2-K
  • [4] Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity
    Bickerstaff, MCM
    Botto, M
    Hutchinson, WL
    Herbert, J
    Tennent, GA
    Bybee, A
    Mitchell, DA
    Cook, HT
    Butler, PJG
    Walport, MJ
    Pepys, MB
    [J]. NATURE MEDICINE, 1999, 5 (06) : 694 - 697
  • [5] Serum amyloid P component binds to late apoptotic cells and mediates their uptake by monocyte-derived macrophages
    Bijl, M
    Horst, G
    Bijzet, J
    Bootsma, H
    Limburg, PC
    Kallenberg, CGM
    [J]. ARTHRITIS AND RHEUMATISM, 2003, 48 (01): : 248 - 254
  • [6] DERIVATION OF THE SLEDAI - A DISEASE-ACTIVITY INDEX FOR LUPUS PATIENTS
    BOMBARDIER, C
    GLADMAN, DD
    UROWITZ, MB
    CARON, D
    CHANG, CH
    [J]. ARTHRITIS AND RHEUMATISM, 1992, 35 (06): : 630 - 640
  • [7] Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies
    Botto, M
    Dell'Agnola, C
    Bygrave, AE
    Thompson, EM
    Cook, HT
    Petry, F
    Loos, M
    Pandolfi, PP
    Walport, MJ
    [J]. NATURE GENETICS, 1998, 19 (01) : 56 - 59
  • [8] Reduced expression of CD44 on monocytes and neutrophils in systemic lupus erythematosus: relations with apoptotic neutrophils and disease activity
    Cairns, AP
    Crockard, AD
    McConnell, JR
    Courtney, PA
    Bell, AL
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 2001, 60 (10) : 950 - 955
  • [9] AUTOANTIGENS TARGETED IN SYSTEMIC LUPUS-ERYTHEMATOSUS ARE CLUSTERED IN 2 POPULATIONS OF SURFACE-STRUCTURES ON APOPTOTIC KERATINOCYTES
    CASCIOLAROSEN, LA
    ANHALT, G
    ROSEN, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (04) : 1317 - 1330
  • [10] Complement C4 inhibits systemic autoimmunity through a mechanism independent of complement receptors CR1 and CR2
    Chen, ZB
    Koralov, SB
    Kelsoe, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (09) : 1339 - 1351