Annexin A2 Enhances Complement Activation by Inhibiting Factor H.

Area of Science:

• Immunology
• Complement System
• Protein-Protein Interactions

Background:

• Factor H is crucial for regulating the alternative pathway (AP) of complement activation.
• Dysregulation of the AP is linked to various diseases.
• Local tissue conditions, not just genetic factors, may influence factor H function.

Purpose of the Study:

• To investigate if inducible proteins in tissues can impair factor H's ability to control the AP.
• To identify factor H binding partners in kidney tissue that might affect its function.

Main Methods:

• Immunoprecipitation of murine factor H from mouse kidneys.
• Immunoaffinity liquid chromatography-mass spectrometry to identify binding partners.
• In vitro and in vivo experiments using recombinant annexin A2 to assess its effect on factor H function and complement activation.
• Murine model of acute pneumococcal otitis media to evaluate annexin A2's role in bacterial clearance.

Main Results:

• Annexin A2 was identified as a novel binding partner of factor H.
• Annexin A2 was shown to reduce factor H binding to cell surfaces.
• Recombinant annexin A2 impaired factor H-mediated complement regulation and enhanced complement activation in vitro and in vivo.
• In a model of bacterial infection, annexin A2 administration improved bacterial opsonization and clearance.

Conclusions:

• Local production of annexin A2 in tissues suppresses factor H's regulatory control over the AP.
• Annexin A2 contributes to AP-mediated inflammation by locally impairing factor H function.
• Annexin A2 also plays a beneficial role by enhancing complement-mediated bacterial clearance.