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Surface complement C3 fragments and cellular binding of microparticles in patients with SLE
Line Kjær Winberg1, Claus Henrik Nielsen1, Søren Jacobsen1
1Institute for Inflammation Research and Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Lupus Science & Medicine
|April 15, 2017
Summary
Microparticles (MPs) in systemic lupus erythematosus (SLE) patients show altered complement component 3 (C3) fragment composition and increased binding to phagocytes. This suggests defective clearance of apoptotic material contributes to SLE pathogenesis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by impaired clearance of apoptotic material.
- Microparticles (MPs) are small vesicles released from cell membranes, implicated in various pathological processes.
- Complement component 3 (C3) plays a crucial role in immune responses and clearance mechanisms.
Purpose of the Study:
- To investigate the characteristics of MPs in SLE patients compared to healthy controls (HCs).
- To determine the cellular origin, C3 fragment deposition, and binding capacity of MPs to phagocytes and erythrocytes.
- To explore the relevance of these MP features in the pathogenesis and clearance of apoptotic material in SLE.
Main Methods:
- Analysis of C3 fragment deposition (C3b, iC3b, C3d) on MPs using specific antibodies.
- Assessment of MP membrane integrity and cell surface markers via 7-aminoactinomycin D (7AAD) and annexin V staining.
- Flow cytometry to evaluate the binding of fluorescently labeled MPs to autologous phagocytes and erythrocytes in the presence of serum.
Main Results:
- MPs from SLE patients exhibited a higher proportion of C3 fragments but lower levels of opsonising C3b/iC3b compared to HCs.
- C3b/iC3b levels on MPs correlated with circulating C3 concentrations in SLE patients.
- Granulocytes from SLE patients bound significantly more autologous MPs than those from HCs, with erythrocytes inhibiting this binding.
Conclusions:
- Altered C3 fragment composition and increased MP binding to phagocytes in SLE patients suggest defective clearance of apoptotic material.
- Both MP opsonisation and cellular binding dynamics are implicated as critical factors in the pathogenesis of SLE.
- These findings highlight potential mechanisms contributing to disease progression and offer targets for therapeutic interventions.