Complement activation induced by human C-reactive protein in mildly acidic conditions

Area of Science:

• Immunology
• Biochemistry

Background:

• Human C-reactive protein (CRP) typically activates the complement system via specific ligands.
• Inflammatory sites often exhibit mildly acidic conditions.

Purpose of the Study:

• To investigate the mechanism of complement activation by CRP under non-ligand-dependent conditions.
• To determine the role of pH and surface properties in CRP-mediated complement activation.

Main Methods:

• Complement activation assays at varying pH levels.
• Analysis of complement component consumption (C1, C4, C2, C3, C5).
• Surface interaction studies using different tube materials and kaolin.
• Circular dichroism and fluorescence spectroscopy to assess CRP conformational changes.

Main Results:

• CRP induced complement activation at a pH optimum of 6.3, characteristic of inflammatory environments.
• Activation followed the classical pathway, primarily consuming early components (C1, C4, C2, C3) with minimal C5 consumption.
• Activation required negatively charged surfaces, as evidenced by differential reaction in glass versus polypropylene tubes and restoration with kaolin.
• CRP exhibited pH-dependent conformational changes affecting its interaction with the complement system.

Conclusions:

• CRP can activate the complement system in a ligand-independent manner under mildly acidic conditions.
• This activation is mediated by the early, classical pathway and is influenced by pH-induced conformational changes in CRP and surface charge.
• Findings suggest a novel mechanism for complement activation at inflammatory sites.