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Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial.

Authors: De Boer, JD  Berger, M  Majoor, CJ  Kager, LM  Meijers, JC  Terpstra, S  Nieuwland, R  Boing, AN  Lutter, R  Wouters, D  Van Mierlo, GJ  Zeerleder, SS  Bel, EH  Van't Veer, C  De Vos, AF  Van der Zee, JS  Van der Poll, T 
Citation: de Boer JD, etal., Eur Respir J. 2015 Dec;46(6):1636-44. doi: 10.1183/13993003.00459-2015. Epub 2015 Sep 17.
Pubmed: (View Article at PubMed) PMID:26381519
DOI: Full-text: DOI:10.1183/13993003.00459-2015

Asthma patients show evidence of a procoagulant state in their airways, accompanied by an impaired function of the anticoagulant protein C system. We aimed to study the effect of recombinant human activated protein C (rhAPC) in allergic asthma patients.We conducted a randomised, double-blind, placebo-controlled, proof-of-concept study in house dust mite (HDM) allergic asthma patients. Patients were randomised to receive intravenous rhAPC (24 microg.kg(-1).h(-1); n=12) or placebo (n=12) for 11 h. 4 h after the start of infusion, a first bronchoscopy was performed to challenge one lung segment with saline (control) and a contralateral segment with a combination of HDM extract and lipopolysaccharide (HDM+LPS), thereby mimicking environmental house dust exposure. A second bronchoscopy was conducted 8 h after intrabronchial challenge to obtain bronchoalveolar lavage fluid (BALF).rhAPC did not influence HDM+LPS induced procoagulant changes in the lung. In contrast, rhAPC reduced BALF leukocyte counts by 43% relative to placebo, caused by an inhibitory effect on neutrophil influx (64% reduction), while leaving eosinophil influx unaltered. rhAPC also reduced neutrophil degranulation products in the airways.Intravenous rhAPC attenuates HDM+LPS-induced neutrophil migration and protein release in allergic asthma patients by an effect that does not rely on coagulation inhibition.

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CRRD Object Information
CRRD ID: 11099992
Created: 2016-06-10
Species: All species
Last Modified: 2016-06-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.