RT Journal Article
SR Electronic
T1 Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP ERJ-00459-2015
DO 10.1183/13993003.00459-2015
A1 J. Daan de Boer
A1 Marieke Berger
A1 Christof J. Majoor
A1 Liesbeth M. Kager
A1 Joost C.M. Meijers
A1 Sanne Terpstra
A1 Rienk Nieuwland
A1 Anita N. Boing
A1 René Lutter
A1 Diana Wouters
A1 Gerard J. van Mierlo
A1 Sacha S. Zeerleder
A1 Elisabeth H. Bel
A1 Cornelis van't Veer
A1 Alex F. de Vos
A1 Jaring S. van der Zee
A1 Tom van der Poll
YR 2015
UL http://erj.ersjournals.com/content/early/2015/09/17/13993003.00459-2015.abstract
AB 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 µg·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.Recombinant activated protein C attenuates allergen-induced migration of neutrophils to the bronchoalveolar space of asthma patients http://ow.ly/Rsevw