The C-terminus of complement factor H is essential for host cell protection

Area of Science:

• Immunology
• Cell Biology

Background:

• The complement system is a key part of innate immunity that eliminates microbes.
• Factor H (FH) is a plasma protein that regulates complement and protects host tissues.
• Endothelial cells have membrane-bound complement regulators.

Purpose of the Study:

• To investigate the role of cell-surface-bound Factor H in regulating complement activation on endothelial cells.
• To determine the importance of the Factor H C-terminus in its interaction with host cells.

Main Methods:

• Studied the regulatory activity of Factor H on endothelial cells.
• Used monoclonal antibodies to block the C-terminus of Factor H.
• Enzymatically removed membrane regulators CD55 and CD59.
• Assessed complement activation, C3b deposition, and membrane attack complex formation.

Main Results:

• Cell-bound Factor H significantly contributes to complement regulation at the cell surface.
• Blocking the Factor H C-terminus inhibited cell binding and increased complement activation.
• Absence of Factor H led to increased C3b deposition and membrane attack complexes.
• Removal of CD55/CD59 enhanced complement-mediated lysis in the absence of Factor H.

Conclusions:

• Factor H plays a critical, underestimated role in complement control at cellular surfaces.
• The C-terminus of Factor H is essential for host cell recognition and protection.
• Surface-bound Factor H is vital for preventing complement-mediated damage to host cells.