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Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors.
BMC Res Notes 2019; 12(1):291BR

Abstract

OBJECTIVE

We recently investigated the pathways of immunoreactive bradykinin (iBK) formation in fresh blood of normal volunteers and of patients with hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-1/-2). Herein, we adapted the techniques to small volumes (200 μl) of previously frozen citrated plasma and further analyzed the mechanisms of iBK formation with additional biotechnological inhibitors.

RESULTS

Measurable iBK formation was observed under stimulation with tissue kallikrein (KLK-1, 10 nM), the particulate material Kontact-APTT (concentration reduced to 2% v/v) or recombinant tissue plasminogen activator (tPA, 169 nM), with little background in unstimulated plasma incubated for up to 2 h. Plasma samples from HAE-1/-2 patients responded earlier to tPA than those from controls, as previously reported with whole blood. Lanadelumab inhibited iBK formation induced by Kontact-APTT and tPA. A highly specific plasmin inhibitor, DX-1000, abolished tPA-induced iBK formation in plasma but had no effect against Kontact-APTT, confirming the role of fibrinolysis in tPA-induced kinin formation. The anti-lanadelumab neutralizing antibody M293-D02 reversed the inhibitory effects of lanadelumab. Frozen plasma is a suitable material for measuring iBK formation kinetics, with possible applications such as investigating the effect of rare disease states on the kallikrein-kinin system and monitoring the effect of HAE prophylactic treatments.

Authors+Show Affiliations

Axe Microbiologie-Infectiologie et Immunologie, CHU de Québec-Université Laval, Quebec, QC, G1V 4G2, Canada. francois.marceau@crchudequebec.ulaval.ca.Axe Endocrinologie et Néphrologie, CHU de Québec-Université Laval, Quebec, QC, G1V 4G2, Canada.Division of Hematology/Oncology, CHU Ste-Justine, Montreal, QC, H3T 1C5, Canada.Service d'allergie, CHU de Québec-Université Laval, Quebec, QC, G1V 4G2, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31133046

Citation

Marceau, François, et al. "Increased Fibrinolysis-induced Bradykinin Formation in Hereditary Angioedema Confirmed Using Stored Plasma and Biotechnological Inhibitors." BMC Research Notes, vol. 12, no. 1, 2019, p. 291.
Marceau F, Bachelard H, Rivard GÉ, et al. Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors. BMC Res Notes. 2019;12(1):291.
Marceau, F., Bachelard, H., Rivard, G. É., & Hébert, J. (2019). Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors. BMC Research Notes, 12(1), p. 291. doi:10.1186/s13104-019-4335-8.
Marceau F, et al. Increased Fibrinolysis-induced Bradykinin Formation in Hereditary Angioedema Confirmed Using Stored Plasma and Biotechnological Inhibitors. BMC Res Notes. 2019 May 27;12(1):291. PubMed PMID: 31133046.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased fibrinolysis-induced bradykinin formation in hereditary angioedema confirmed using stored plasma and biotechnological inhibitors. AU - Marceau,François, AU - Bachelard,Hélène, AU - Rivard,Georges-Étienne, AU - Hébert,Jacques, Y1 - 2019/05/27/ PY - 2019/03/07/received PY - 2019/05/22/accepted PY - 2019/5/29/entrez PY - 2019/5/28/pubmed PY - 2019/5/28/medline KW - Bradykinin KW - Fibrinolysis KW - Hereditary angioedema with C1-INH deficiency KW - Kallikreins KW - Lanadelumab SP - 291 EP - 291 JF - BMC research notes JO - BMC Res Notes VL - 12 IS - 1 N2 - OBJECTIVE: We recently investigated the pathways of immunoreactive bradykinin (iBK) formation in fresh blood of normal volunteers and of patients with hereditary angioedema due to C1-esterase inhibitor deficiency (HAE-1/-2). Herein, we adapted the techniques to small volumes (200 μl) of previously frozen citrated plasma and further analyzed the mechanisms of iBK formation with additional biotechnological inhibitors. RESULTS: Measurable iBK formation was observed under stimulation with tissue kallikrein (KLK-1, 10 nM), the particulate material Kontact-APTT (concentration reduced to 2% v/v) or recombinant tissue plasminogen activator (tPA, 169 nM), with little background in unstimulated plasma incubated for up to 2 h. Plasma samples from HAE-1/-2 patients responded earlier to tPA than those from controls, as previously reported with whole blood. Lanadelumab inhibited iBK formation induced by Kontact-APTT and tPA. A highly specific plasmin inhibitor, DX-1000, abolished tPA-induced iBK formation in plasma but had no effect against Kontact-APTT, confirming the role of fibrinolysis in tPA-induced kinin formation. The anti-lanadelumab neutralizing antibody M293-D02 reversed the inhibitory effects of lanadelumab. Frozen plasma is a suitable material for measuring iBK formation kinetics, with possible applications such as investigating the effect of rare disease states on the kallikrein-kinin system and monitoring the effect of HAE prophylactic treatments. SN - 1756-0500 UR - https://www.unboundmedicine.com/medline/citation/31133046/Increased_fibrinolysis-induced_bradykinin_formation_in_hereditary_angioedema_confirmed_using_stored_plasma_and_biotechnological_inhibitors L2 - https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-019-4335-8 DB - PRIME DP - Unbound Medicine ER -