Tags

Type your tag names separated by a space and hit enter

Activated human platelets induce factor XIIa-mediated contact activation.
Biochem Biophys Res Commun. 2010 Jan 01; 391(1):11-7.BB

Abstract

Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation, in the presence of a negatively charge substance or material. Still proof is lacking that FXII is activated by platelets in a more physiological environment. In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood. Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thrombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed, demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation. Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected on activated platelets. Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated. Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time. We conclude that platelet activation triggers FXII-mediated contact activation on the surface and in the vicinity of activated platelets. This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation. Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation.

Authors+Show Affiliations

Departments of Oncology, Radiology, and Clinical Immunology, Division of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, SE-751 85 Uppsala, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19878657

Citation

Bäck, Jennie, et al. "Activated Human Platelets Induce Factor XIIa-mediated Contact Activation." Biochemical and Biophysical Research Communications, vol. 391, no. 1, 2010, pp. 11-7.
Bäck J, Sanchez J, Elgue G, et al. Activated human platelets induce factor XIIa-mediated contact activation. Biochem Biophys Res Commun. 2010;391(1):11-7.
Bäck, J., Sanchez, J., Elgue, G., Ekdahl, K. N., & Nilsson, B. (2010). Activated human platelets induce factor XIIa-mediated contact activation. Biochemical and Biophysical Research Communications, 391(1), 11-7. https://doi.org/10.1016/j.bbrc.2009.10.123
Bäck J, et al. Activated Human Platelets Induce Factor XIIa-mediated Contact Activation. Biochem Biophys Res Commun. 2010 Jan 1;391(1):11-7. PubMed PMID: 19878657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activated human platelets induce factor XIIa-mediated contact activation. AU - Bäck,Jennie, AU - Sanchez,Javier, AU - Elgue,Graciela, AU - Ekdahl,Kristina Nilsson, AU - Nilsson,Bo, Y1 - 2009/10/28/ PY - 2009/10/20/received PY - 2009/10/23/accepted PY - 2009/11/3/entrez PY - 2009/11/3/pubmed PY - 2010/3/17/medline SP - 11 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 391 IS - 1 N2 - Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation, in the presence of a negatively charge substance or material. Still proof is lacking that FXII is activated by platelets in a more physiological environment. In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood. Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thrombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed, demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation. Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected on activated platelets. Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated. Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time. We conclude that platelet activation triggers FXII-mediated contact activation on the surface and in the vicinity of activated platelets. This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation. Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/19878657/Activated_human_platelets_induce_factor_XIIa_mediated_contact_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(09)02114-7 DB - PRIME DP - Unbound Medicine ER -