Abstract
Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing. PF4 is stored in platelet α-granules bound to the glycosaminoglycan (GAG) chains of serglycin. This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains. Additionally, PF4 had a higher affinity for endothelial-derived perlecan heparan sulfate chains than serglycin GAG chains. The binding of PF4 to perlecan was found to inhibit both FGF2 signaling and platelet activation. This study revealed additional insight into the ways in which PF4 interacts with components of the vasculature to modulate cellular events.
Highlights
Platelet factor 4 (PF4) is produced by platelets with roles in both inflammation and wound healing
This study revealed that platelet serglycin is decorated with chondroitin/dermatan sulfate and that PF4 binds to these GAG chains
Treatment of the serglycin with chondroitinase (C’ase) ABC to digest GAG chains containing both CS and DS disaccharides resulted in a reduction of the Mr of the smear to ϳ25,000, corresponding to the protein core indicating that platelet-derived serglycin contained ϳ45,000 – 225,000 CS and/or DS (Fig. 1A, second lane)
Summary
P10124 a MOWSE score as determined by Mascot query. This is the value (P) that is a measure of the probability that the match is a random event expressed as Ϫ10log(P). The higher the score, the more confidence that the match is not due to a random event. Serglycin GAG chains and can be competed from complexes with serglycin in the presence of perlecan. The binding of PF4 to perlecan inhibits both FGF signaling and platelet activation
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