The binding of protein S and the protein S-C4BP complex to neutrophils is apoptosis dependent.

Vitamin K-dependent protein S and complement regulator C4b-binding protein (C4BP) form a high-affinity complex in plasma. We have previously shown that both free protein S and the C4BP-protein S complex can bind to apoptotic Jurkat cells. It has been demonstrated in the past that protein S and C4BP can bind to neutrophils.

Role of CCP2 of the C4b-binding protein beta-chain in protein S binding evaluated by mutagenesis and monoclonal antibodies.

Complement regulator C4b-binding protein (C4BP) and the anticoagulant vitamin K-dependent protein S form a high affinity complex in human plasma. C4BP is composed of seven alpha-chains and a unique beta-chain, each chain comprising repeating complement control protein (CCP) modules. The binding site for protein S mainly involves the first of the three beta-chain CCPs (CCP1).

Vitamin K-dependent protein S localizing complement regulator C4b-binding protein to the surface of apoptotic cells.

Apoptosis is characterized by a lack of inflammatory reaction in surrounding tissues, suggesting local control of complement activation. During the initial stage of apoptosis, cells expose negatively charged phospholipid phosphatidylserine on their surfaces. The vitamin K-dependent protein S has a high affinity for this type of phospholipid.