Apoptosis of Peripheral Blood Leukocytes in Systemic Lupus Erythematosus: Studies on Serum Induction and Complement-Dependent Clearance Mechanisms
Author
Summary, in English
(Papers I and II) We found that the apoptosis inducing effect was specific for sera from SLE patients when comparing with sera from various control groups. However, the apoptosis inducing effect was not related to SLE disease activity. Serum from SLE patients was demonstrated to induce classical caspase-dependent apoptosis in monocytes and lymphocytes. The apoptosis induction was not dependent on death receptors but involvement of the mitochondrial pathway was indicated.
(Paper III) Phagocytosis of apoptotic cells by macrophages and C3 deposition on apoptotic cells were investigated in the presence of sera lacking different complement proteins. We found that complement-mediated opsonisation and phagocytosis of apoptotic cells, particularly those undergoing secondary necrosis, are dependent mainly upon an intact classical pathway. C1q was not more important than other classical pathway components, suggesting a role in other pathogenetic processes than defect clearance of apoptotic cells.
(Paper IV) We evaluated the roles of serum complement and antibodies against histones in relation to phagocytosis of necrotic cell material by polymorphonuclear neutrophil granulocytes (PMNs). Phagocytosis of necrotic material by PMNs and high concentration of antibodies against a broad spectrum of histones correlated with active SLE disease. The specificities of these anti-histone antibodies appear to determine the complement-dependent phagocytosis.
In conclusion, sera from SLE patients have the capacity to contribute to an increased load of apoptotic cells. An efficient clearance of apoptotic and necrotic cell material is dependent on a functional classical pathway, and autoantibodies against histones reflect the presence of apoptotic or necrotic cells contributing to the autoimmune process in SLE.
Publishing year
2010
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2010:22
Full text
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Document type
Dissertation
Publisher
Department of Laboratory Medicine, Lund University
Topic
- Immunology in the medical area
- Microbiology in the medical area
Keywords
- Complement
- Apoptosis
- SLE
- Autoimmunity
Status
Published
Supervisor
- Lennart Truedsson
- Anders Bengtsson
- Gunnar Sturfelt
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86443-36-8
Defence date
14 April 2010
Defence time
09:00
Defence place
Segerfalksalen, Wallenberg neurocenter BMC
Opponent
- Cees van Kooten (Professor)