Binding of fibronectin by the acute phase reactant C-reactive protein

Area of Science:

• Biochemistry
• Immunology
• Materials Science

Background:

• C-reactive protein (CRP) levels rise in plasma after tissue injury.
• Fibronectin levels often decrease in plasma following tissue injury.
• The interaction between CRP and fibronectin in vivo is not fully understood.

Purpose of the Study:

• To investigate the binding interaction between immobilized C-reactive protein (CRP) and soluble plasma fibronectin.
• To characterize the conditions influencing CRP-fibronectin binding.
• To elucidate the functional implications of this interaction in the context of tissue repair.

Main Methods:

• Immobilization of CRP onto polystyrene surfaces.
• Binding assays with soluble human plasma fibronectin under varying ionic conditions, pH, and presence of divalent cations.
• Competition assays using fibrinogen and albumin.
• Characterization of the fibronectin-binding domain using fragmentation.

Main Results:

• Immobilized CRP binds soluble fibronectin with high affinity (Kd = 1.5 X 10(-8) M).
• Binding is sensitive to ionic strength, pH (enhanced at acidic pH), and inhibited by Ca2+ ions (>1 mM).
• Fibrinogen competes for CRP binding sites, explaining differential binding from serum vs. plasma; CRP density and surface blocking affect binding.

Conclusions:

• CRP immobilized on surfaces can bind fibronectin, suggesting a role in modulating extracellular matrix during inflammation.
• The binding interaction is specific and influenced by physiological conditions, providing a link between acute phase proteins and tissue repair mechanisms.
• A specific fragment of fibronectin (120-140 kDa) contains the CRP-binding activity, which also includes cell-binding and heparin-binding domains.