Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death

Abstract

The phagocytosis of dying cells is an integral feature of apoptosis and necrosis. There are many receptors involved in recognition of dying cells, however, the molecular mechanisms of the scavenging process remain elusive. The activation by necrotic cells of complement is well established, however, the importance of complement in the scavenging process of apoptotic cells was just recently described. Here we report that the complement components C3 and C4 immediately bound to necrotic cells. The binding of complement was much higher for lymphocytes compared to granulocytes. In case of apoptotic cell death complement binding was a rather late event, which in lymphocytes was preceded by secondary necrosis. Taken together complement binding is an immediate early feature of necrosis and a rather late event during apoptotic cell death. We conclude that complement may serve as an opsonin for fragments of apoptotic cells that have escaped regular scavenging mechanisms.

Apoptosis and necrosis mediate skeletal muscle fiber loss in age‐induced mitochondrial enzymatic abnormalities

“…This assembly of complement components occurs primarily in early stages of necrosis (Gaipl et al ., 2001) and allows for macrophage infiltration into the damaged fiber. We observed a significant increase in the number of fibers positive for necrosis markers (C5b‐9 and CD68) in aged skeletal muscle.…”

Cooperation between C1q and DNase I in the clearance of necrotic cell–derived chromatin

“…The classical pathway complement component C1q can directly bind via its globular heads to the surface of apoptotic cells (14) and to blebs derived from apoptotic cells (58). The binding of C3 and C4 to apoptotic cells (16) has recently been shown, especially in the very late phases of the suicide process (18). We were interested to determine whether complement components other than those acting as opsonins also contribute to the degradation processes of necrotic cellderived chromatin.…”

“…The binding of C1q, which is found in low levels in some patients with SLE, to apoptotic cells was first described by Ahearn and colleagues (14,15), and the importance of complement in the scavenging process is becoming more and more evident. Several studies have suggested an association between the classical complement pathway and the clearance of early apoptotic and secondary necrotic cells (14,(16)(17)(18).…”

“…The role of complement and other adaptor molecules in the opsonization and clearance of apoptotic cells has been established (14,16,18,20,21). During apoptosis, chromatin is degraded by internal proteases and nucleases before the cells lose their membrane integrity.…”

Disposal of dying cells: A balancing act between infection and autoimmunity

“…Usually, apoptotic cells are cleared in the early phase of cell death. However, recent studies showed that some backup mechanisms may exist that enable the safe removal of late apoptotic cells that have escaped regular, early scavenging (47,64,65). When the recognition system of the phagocytes fails, "danger" may be overcome, "safety" may be illusory, and autoimmunity and infection result.…”