Complement activation by phospholipids: the interplay of factor H and C1q

Area of Science:

• Immunology
• Complement System Biology

Background:

• Complement proteins recognize charged particles like anionic phospholipids (aPL).
• C1q activates the classical complement pathway, while factor H inhibits the alternative pathway.
• aPL, such as cardiolipin, bind both C1q and factor H.

Purpose of the Study:

• To investigate the opposing effects of C1q and factor H on complement activation by aPL.
• To determine if factor H regulates the classical complement pathway.

Main Methods:

• Surveying C1q and factor H binding to aPL coated on microtitre plates or in liposomes.
• Measuring complement activation by aPL.
• Adjusting the C1q:factor H molar ratio in human sera to measure C4 activation.

Main Results:

• Both C1q and factor H bound to all tested aPL and competed for binding.
• aPL activated the classical pathway but negligibly the alternative pathway.
• Factor H directly regulated classical pathway activation by competing with C1q for aPL binding.

Conclusions:

• Factor H acts as a direct regulator of the classical complement pathway by inhibiting C1q binding to aPL.
• This regulatory mechanism is distinct from factor H's role in the alternative pathway.
• Factor H has a novel role in downregulating classical complement pathway activation by aPL.