Complement Membrane Attack Complex: New Roles, Mechanisms of Action, and Therapeutic Targets
Catherine B Xie1, Dan Jane-Wit2, Jordan S Pober1
1Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.
The American Journal of Pathology
|March 21, 2020
Summary
The complement membrane attack complex (MAC) can cause cell death or trigger inflammatory signaling. New research reveals MAC
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- The complement system's membrane attack complex (MAC) is a key immune effector.
- MAC traditionally induces cell lysis by forming pores in cell membranes.
- Nucleated cells possess defense mechanisms against MAC-induced cytolysis.
Purpose of the Study:
- To explore novel functions of MAC beyond cytolysis.
- To investigate MAC's role in intracellular signaling and cell activation.
- To update understanding of MAC's contribution to disease pathogenesis.
Main Methods:
- Analysis of MAC structure and biophysical properties.
- Investigation of MAC-induced intracellular signaling pathways.
- Examination of MAC's role in proinflammatory protein expression and inflammasome activation.
Main Results:
- MAC exhibits heterogeneous precursors and conformations influencing its function.
- Non-lytic MAC interactions trigger intracellular signaling and cell activation.
- MAC-activated cells exhibit proinflammatory responses, including NF-κB activation and IL-1β/IL-18 secretion.
Conclusions:
- MAC's functions extend beyond cytolysis to include significant roles in cell signaling and inflammation.
- Understanding MAC-mediated signaling pathways offers new therapeutic targets.
- Targeting MAC assembly, signaling, and proinflammatory effects may benefit complement-mediated diseases.
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