page 1937. Trouw and colleagues now show that C4BP and its binding partner, anticoagulant protein S (PS), cooperate to grab onto necrotic cells and to inhibit the release of cellular DNA.
C4BP short-circuits the complement cascade by binding to the activated complement components C3b and C4b and presenting them to the proteolytic complement inhibitor Factor I for degradation. This inhibitory capacity of C4BP can be coopted by bacterial pathogens, which coat themselves with this protein to avoid complement-mediated destruction by phagocytic cells.
This group recently identified a role for the C4BP–PS complex: it binds to apoptotic cells through the phosphatidylserine-binding domain of PS. This association could prevent the deposition and activation of complement on the surface of the apoptotic cells, allowing the dying cells to be removed without provoking an inflammatory response.
Trouw et al. now show that C4BP-PS complexes bind to necrotic cells in the same manner. This binding limited complement deposition and decreased the capacity of necrotic cells to induce inflammatory cytokine production by macrophages. Once bound to necrotic cells via PS, C4BP could bind and trap cellular DNA as it leaked out of the dying cells. The authors suggest that this function of C4BP may be critical for host protection from autoimmunity, as free DNA can trigger inflammation and elicit the production of anti-DNA antibodies.