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J. Exp. Med.,
Volume 188, Number 12, December 21, 1998 2313-2320
By
From the Hospital for Special Surgery, Cornell University Medical College, New York 10021
Apoptotic cells are rapidly engulfed by phagocytes, but the receptors and ligands responsible for
this phenomenon are incompletely characterized. Previously described receptors on blood-
derived macrophages have been characterized in the absence of serum and show a relatively
low uptake of apoptotic cells. Addition of serum to the phagocytosis assays increased the uptake
of apoptotic cells by more than threefold. The serum factors responsible for enhanced uptake
were identified as complement components that required activation of both the classical pathway and alternative pathway amplification loop. Exposure of phosphatidylserine on the apoptotic cell surface was partially responsible for complement activation and resulted in coating the
apoptotic cell surface with C3bi. In the presence of serum, the macrophage receptors for C3bi,
CR3 (CD11b/CD18) and CR4 (CD11c/CD18), were significantly more efficient in the uptake of apoptotic cells compared with previously described receptors implicated in clearance.
Complement activation is likely to be required for efficient uptake of apoptotic cells within the
systemic circulation, and early component deficiencies could predispose to systemic autoimmunity by enhanced exposure to and/or aberrant deposition of apoptotic cells.
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