Novel interaction of properdin and coagulation factor XI: Crosstalk between complement and coagulation

Area of Science:

• Biochemistry
• Immunology
• Hematology

Background:

• Crosstalk between complement and coagulation cascades can cause thromboinflammatory events.
• Both pathways interact with anionic surfaces like glycosaminoglycans.
• No prior evidence linked properdin (FP), a complement regulator, to coagulation factor XI (FXI) or FXIa.

Purpose of the Study:

• Investigate potential crosstalk between properdin (FP) and the intrinsic coagulation pathway.
• Determine the functional consequences of this interaction on blood coagulation.

Main Methods:

• Established chromogenic assays to study FXI autoactivation and FXIa kinetics.
• Utilized SDS-PAGE and LC-MS to analyze substrate specificity and cleavage.
• Employed surface plasmon resonance (SPR) to confirm direct binding between FP and FXIa.

Main Results:

• Identified a novel interaction between properdin (FP) and activated factor XI (FXIa).
• Demonstrated that FP modulates FXIa activity and FXIa can cleave FP.
• Confirmed high-affinity binding of FXI and FXIa to FP, influencing FX activation.

Conclusions:

• Properdin (FP) directly interacts with activated factor XI (FXIa), revealing a novel link between complement and coagulation.
• This interaction influences key steps in the intrinsic coagulation pathway.
• Findings suggest a new mechanism for intercommunication between the complement and coagulation systems in thromboinflammation.