Myeloperoxidase influences the complement regulatory function of modified C-reactive protein

Area of Science:

• Immunology
• Complement System Biology

Background:

• Active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by elevated C-reactive protein (CRP).
• CRP can inhibit the alternative complement pathway and activate the classical complement pathway, while the alternative pathway is crucial in AAV pathogenesis.

Purpose of the Study:

• To investigate the interaction between myeloperoxidase (MPO) and C-reactive protein (CRP) in the context of AAV.
• To determine if MPO influences CRP's interaction with complement components like Factor H and C1q.

Main Methods:

• Purified MPO and MPO released from ANCA-stimulated neutrophils were used.
• Binding assays were performed to assess interactions between MPO, modified CRP (mCRP), pentameric CRP, Factor H, and C1q.
• MPO enzymatic activity and binding to its inhibitors (ceruloplasmin, MPO-ANCA) were evaluated after mCRP binding.

Main Results:

• Both purified and neutrophil-released MPO bound to mCRP, but not to pentameric CRP.
• MPO inhibited the binding of mCRP to both Factor H and C1q.
• MPO's enzymatic activity and binding to ceruloplasmin or MPO-ANCA were unaffected by mCRP.

Conclusions:

• Myeloperoxidase (MPO) interacts with modified C-reactive protein (mCRP) in AAV.
• MPO may act as a complement regulator by blocking mCRP's inhibitory effects on the alternative complement pathway.