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Complement-dependent clearance of apoptotic cells by human macrophages
D Mevorach1, J O Mascarenhas, D Gershov
1Hospital for Special Surgery, Cornell University Medical College, New York 10021, USA.elkonk@hss.edu
The Journal of Experimental Medicine
|December 22, 1998
Summary
Serum complement components significantly enhance phagocyte uptake of apoptotic cells, primarily through C3bi coating and CR3/CR4 receptor activation. This highlights the crucial role of complement in efficient cellular debris clearance.
Area of Science:
- Immunology
- Cell Biology
Background:
- Phagocytic clearance of apoptotic cells is vital for tissue homeostasis.
- Existing knowledge of receptors involved in apoptotic cell uptake is incomplete, especially in physiological conditions like the presence of serum.
Purpose of the Study:
- To identify serum factors and macrophage receptors responsible for efficient phagocytosis of apoptotic cells.
- To elucidate the mechanisms by which serum enhances apoptotic cell clearance.
Main Methods:
- Phagocytosis assays using blood-derived macrophages and apoptotic cells.
- Addition of serum and analysis of complement pathway involvement (classical and alternative).
- Identification of complement components (C3bi) and macrophage receptors (CR3, CR4) mediating uptake.
Main Results:
- Serum addition increased apoptotic cell uptake by over threefold.
- Complement activation, involving both classical and alternative pathways, was essential for this enhancement.
- Phosphatidylserine exposure on apoptotic cells initiated complement activation, leading to C3bi coating.
- Macrophage receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) showed significantly higher efficiency in C3bi-coated apoptotic cell uptake.
Conclusions:
- Complement activation, particularly via C3bi opsonization, is critical for efficient apoptotic cell clearance in the systemic circulation.
- Deficiencies in early complement components may impair apoptotic cell clearance, potentially leading to autoimmunity due to increased exposure to or aberrant deposition of apoptotic cells.