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Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
Published on: May 24, 2019
Monocyte activation by apoptotic cells removal in systemic lupus erythematosus patients
Lina M Yassin1, Mauricio Rojas, Luis A Ramírez
1Universidad de Antioquia, Medellín, Colombia. yascatorce@yahoo.com
Insights
Systemic lupus erythematosus (SLE) patients show impaired clearance of apoptotic cells (ACs), affecting immune responses. This reduced ACs removal impacts cytokine production and cell surface marker expression differently compared to healthy individuals.
Area of Science:
- Immunology
- Pathogenesis of Autoimmune Diseases
Background:
- Impaired clearance of apoptotic cells (ACs) is implicated in the pathogenesis of systemic lupus erythematosus (SLE).
- Previous studies suggest a role for CD36 in ACs clearance, but its function in SLE patients remains unclear.
Purpose of the Study:
- To investigate the differences in ACs binding, phagocytosis, and subsequent immune responses between SLE patients and healthy controls.
- To explore the role of CD36 and other immune markers in ACs clearance in SLE.
Main Methods:
- Comparative analysis of ACs binding and phagocytosis in SLE patients and healthy controls.
- Assessment of cytokine production (IL-6, CXCL8, CCL22, IL-1β, TNF-α, CCL3) following ACs interaction.
- Evaluation of cell surface marker expression (CD80, CD86, CD36, CD163, HLA-DR) on monocytes and adherent cells.
Main Results:
- SLE patients exhibited decreased binding and phagocytosis of ACs compared to controls.
- ACs interaction induced distinct cytokine profiles in SLE patients versus healthy controls.
- SLE patients showed altered CD80 expression and CD36 downregulation on HLA-DR(+) cells post-ACs removal, unlike controls.
Conclusions:
- Decreased ACs clearance in SLE patients leads to a unique immune response.
- CD36 plays a differential role in ACs clearance between SLE patients and healthy individuals.
- Aberrant immune cell marker expression and cytokine profiles contribute to SLE pathogenesis due to impaired ACs removal.
Abstract:
Decreased apoptotic cells (ACs) removal has been described as relevant in systemic lupus erythematosus (SLE) pathogenesis. Binding/phagocytosis of ACs was decreased in SLE patients. Blocking experiments suggested a role for CD36 in ACs clearance in healthy controls, not observed in SLE patients. Binding/phagocytosis of ACs induced the production of IL-6, CXCL8 and CCL22 in patients and controls and IL-1β, TNF-α and CCL3 only in healthy controls. ACs clearance induced an increase in CD80 and a decrease in CD86 expression in healthy controls and atherosclerotic patients. However, SLE patients did not up-regulate CD80 expression. The number and expression of CD36 and CD163 in monocytes was not different between the groups. ACs removal induced a down-regulation of CD36 expression in adherent HLA-DR(+) cells in SLE patients but not healthy controls. The decreased binding/phagocytosis of ACs observed in SLE patients, induces a distinct immune response compared with healthy controls.
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