Reevaluation of the role of the polar groups of collagen in the platelet-collagen interaction.
Chemical modification of collagen is a tool for exploring the platelet-collagen interaction. Since collagen must polymerize prior to the initiation of platelet aggregation and secretion, modification must be shown to affect platelet-collagen interaction and not collagen-collagen interaction. To address this point, the authors carried out the following chemical modifications on soluble monomeric collagen and preformed fibrillar collagen in parallel: 1) N-and O-acetylation, 2) esterification of the carboxyl groups, 3) succinylation of the free amino groups, 4) esterification of succinylated collagen. Intrinsic viscosity studies of the modified soluble collagens were consistent with normal triple helix conformation. Electron microscopy revealed all modified fibrillar collagen to maintain a fibrillar structure. Platelet aggregation and secretion of 14C-serotonin and platelet factor 4 by soluble and fibrillar collagen, respectively, were studied in human platelet-rich plasma. Neutralization of polar groups by 1) totally abolished aggregation and secretion by both collagens, while blocking acidic groups 2) resulted in enhanced aggregation and secretion by both soluble and fibrillar collagen. Blockage of amino groups by 3) abolished aggregation and secretion by both collagens. Esterified succinylated collagen 4) caused aggregation and secretion at relatively high collagen concentrations. These data support the theory that positive groups of collagen are important in platelet-collagen interaction.
D000107:Acetylation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D055598:Chemical Phenomena; D002621:Chemistry; D003094:Collagen / Q000494:pharmacology*; D004951:Esterification; D006801:Humans; D046911:Macromolecular Substances; D010974:Platelet Aggregation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013387:Succinic Anhydrides / Q000494:pharmacology; D014783:Viscosity
D001779:Blood Coagulation Factors; D046911:Macromolecular Substances; D013387:Succinic Anhydrides; D012701:Serotonin; D010978:Platelet Factor 4; C031801:succinic anhydride; D003094:Collagen