THE PROCOAGULANT ROLE OF NUCLEIC ACIDS IN THE CONTACT SYSTEM

Abstract

Nucleic acids have been identified as procoagulant species in plasma and in vivo animal studies. It is believed that the nucleic acids act as physiological activators of the contact system. However, in order to obtain a better understanding of the role of nucleic acids in the activation of the contact system it is important to analyze and evaluate the individual proteins of the contact system that are stimulated by nucleic acids and identify accompanying proteins required to mediate the nucleic acid-stimulated activation. Previous works suggested that nucleic acids stimulate the activation of factor XII (FXII) in the presence of prekallikrein (PK) and high molecular weight kininogen (HK). In this study we will confirm if both PK and HK are required for nucleic acid-stimulated activation of FXII. We will also study the role of nucleic acids in the activation of PK in the presence or absence of activated FXII (FXIIa) and HK. Previous works also identified that zinc (Zn2+) accelerates surface-mediated activation of FXII by PK and HK, and PK by FXIIa and HK. We will be evaluating zinc’s ability to enhance nucleic acid-stimulated activation of both FXII and PK. We have found that nucleic acids stimulate activation of FXII in the presence of PK and this furthered upon addition of HK. Nucleic acids also stimulate the activation of PK in the presence of FXIIa and this is furthered upon addition of HK. Nucleic acids have stimulated activation of FXII and PK in a dose dependent manner in the presence of the aforementioned accompanying proteins. We have showed that Zn2+ enhances activation of the contact system. Zn2+ enhances nucleic acid-stimulated, PK/HK-mediated activation of FXII. It also enhances nucleic acid-stimulated, FXIIa/HK-mediated activation of PK. These findings enrich our understanding of the role of nucleic acids and zinc in the contact system.