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Zinc-dependent cont...
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Bjorkqvist, JKarolinska Institutet
(författare)
Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
- Artikel/kapitelEngelska2013
Förlag, utgivningsår, omfång ...
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2013-05-01
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Walter de Gruyter GmbH,2013
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:127188513
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http://kipublications.ki.se/Default.aspx?queryparsed=id:127188513URI
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https://doi.org/10.1515/hsz-2013-0144DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Contact to polyanions induces autoactivation of the serine protease factor XII that triggers the kallikrei-kinin system. Recent studies indicate that polysaccharide-induced autoactivation of factor XII has a role in allergy-related vascular leakage, and angioedema. Here, we characterize in vivo effects of the synthetic polysaccharide dextran sulfate in human plasma and in rodent models. Minute amounts of high-molecular-weight dextran sulfate-initiated factor XII-autoactivation and triggered formation of the inflammatory mediator bradykinin via plasma kallikrein-mediated cleavage of high-molecular-weight kininogen. High-molecular-weight kininogen fragments, containing the HKH20 sequence in domain D5H, blocked dextran sulfate-initiated bradykinin-generation by depleting plasma Zn2+ ions. Topical application of high molecular weight dextran sulfate increased leakage in murine skin microvessels, in a bradykinin-dependent manner. Intravital laser scanning microscopy showed a greater than two-fold elevated and accelerated fluid extravasation in C1 esterase inhibitor deficient mice that lack the major inhibitor of factor XII, compared to wild-type controls. Intra-arterial infusion of dextran sulfate induced a rapid transient drop in arterial blood pressure in rats and preinjection of kinin B2 receptor antagonists or HKH20 peptide blunted dextran sulfate-triggered hypotensive reactions. The data characterize dextran sulfate as a potent in vivo activator of factor XII with implications for bradykinin-mediated vascular permeability and blood pressure control.
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lecher, B
(författare)
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Maas, C
(författare)
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Renne, TKarolinska Institutet
(författare)
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Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Biological chemistry: Walter de Gruyter GmbH394:9, s. 1195-12041437-4315
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Ingår i:bchm: Walter de Gruyter GmbH394:9, s. 1195-12041431-6730
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