Читать книгу Immunology - Richard Coico - Страница 100

Cells dying by necrosis can activate complement, leading to C4b and C3b deposition on the cell surface (see Figure 4.7C). The cell is then cleared by interacting with CR1 or CR3 on phagocytic cells. Subcellular membranes, from organelles such as mitochondria and endoplasmic reticulum, also directly activate both classical and alternative pathways and are cleared in a similar way. CRP, the acute‐phase protein and component of the inflammatory response, also binds to damaged and necrotic cells and activates the classical complement pathway. The same structure that CRP binds to on bacterial cell walls—the polysaccharide phosphocholine—is also exposed on damaged and necrotic mammalian cells. Recent evidence also indicates that cells dying as a result of apoptosis may trigger complement activation.

In all these situations, complement removes dead or dying cells from the tissues and contributes to homeostasis. In some conditions, however, complement activation by dead or dying cells may have clinical consequences. Notable examples include complement activation by ischemia and reperfusion. In ischemia, an area of tissue dies after blood and oxygen supplies have been cut (important examples include cardiac muscle after a myocardial infarction or brain tissue following a stroke). Reperfusion is the attempt to restore blood supply to the affected tissue. Complement activation is considered a major contributor to the inflammatory responses associated with both of these states, which damages healthy tissue. Complement‐based therapies are currently being tested to reduce the deleterious effects of the inflammatory response.