Intestinal glycoprotein activates the alternative complement pathway by reacting with factor H.

Area of Science:

• Immunology
• Biochemistry
• Complement System Biology

Background:

• The alternative pathway of the complement system is a critical part of innate immunity.
• Dysregulation of the complement system is implicated in various inflammatory and autoimmune diseases.
• Understanding the molecular mechanisms of complement regulation is essential for therapeutic development.

Purpose of the Study:

• To investigate the mechanism by which a rat intestinal glycoprotein activates the alternative complement pathway.
• To identify the specific complement factors targeted by the glycoprotein.
• To elucidate the role of factors H and I in the glycoprotein-mediated complement activation.

Main Methods:

• Utilized C2-deficient serum to confirm alternative pathway activation.
• Assessed complement factor inactivation and conversion using conglutination assays and immunoelectrophoresis.
• Employed affinity chromatography (epoxy-activated Sepharose 6B) to study factor H binding and retention.

Main Results:

• The rat intestinal glycoprotein fraction substantiated complement activation via the alternative pathway.
• The glycoprotein inhibited the conversion of EAC3b to EAC3bi, indicating interference with complement control factors H and I.
• Factor H was retained by the glycoprotein, and its removal led to spontaneous alternative pathway activation.

Conclusions:

• The rat intestinal glycoprotein activates the alternative complement pathway primarily by inhibiting complement regulatory proteins, specifically factor H.
• The glycoprotein's interaction with factor H disrupts normal complement homeostasis.
• This interaction presents a potential target for modulating complement-mediated inflammation.