C-Reactive Protein Binds to Cholesterol Crystals and Co-Localizes with the Terminal Complement Complex in Human...

Area of Science:

• Immunology
• Cardiovascular Research
• Inflammation Biology

Background:

• Atherosclerosis involves inflammation and complement activation, with cholesterol crystals (CC) implicated in this process.
• Pentraxins like C-reactive protein (CRP), pentraxin 3 (PTX3), and serum amyloid P component (SAP) are linked to cardiovascular risk and interact with the complement system.

Purpose of the Study:

• To investigate whether pentraxins bind to cholesterol crystals (CC) and mediate complement-dependent inflammatory processes.
• To determine the role of CRP, PTX3, and SAP in C1q binding and complement activation on CC.

Main Methods:

• In vitro studies using flow cytometry and fluorescence microscopy to assess pentraxin binding to CC.
• Investigation of C1q binding and complement activation in the presence of pentraxins and CC.
• In vivo analysis of pentraxin and complement complex localization in human atherosclerotic plaques.

Main Results:

• CRP, PTX3, and SAP demonstrated concentration-dependent binding to CC in vitro.
• CRP and PTX3 enhanced C1q binding to CC, with CRP being the most potent mediator of C1q binding and complement activation.
• Phagocytosis of CC was confirmed as complement and C1q-dependent.
• In vivo, CRP, PTX3, and SAP were found in atherosclerotic plaques, but only CRP co-localized with the terminal complement complex C5b-9.

Conclusions:

• C-reactive protein (CRP) acts as a significant recruiter of C1q and facilitator of complement activation on cholesterol crystals (CC).
• These findings highlight a crucial role for CRP in CC-mediated inflammation within atherosclerotic plaques, potentially contributing to disease development.