Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention

In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (8–11, 25–27). For a complete updated view of the MAC structure, the reader is referred to those publications. The observed ring structure apparently corresponds to the structure of polymerized C9 molecules attached to their polymerization accelerator, the C5b-8 complex (28). However, even today we have only a partial view of the fine details of the cytotoxic mechanisms activated by MAC, eventually leading to the point of no return and cell death. Besides the paucity of investigations on the subject, several reasons account for that. First, the early dogmas were based on investigations with complement-targeted artificial membranes and red blood cells, which are clearly different, largely passive targets, compared with nucleated cells (29–34). Second, very large variation exists in refractoriness to the MAC, even among closely related cancer ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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