TY - JOUR T1 - Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00459-2015 SP - ERJ-00459-2015 AU - J. Daan de Boer AU - Marieke Berger AU - Christof J. Majoor AU - Liesbeth M. Kager AU - Joost C.M. Meijers AU - Sanne Terpstra AU - Rienk Nieuwland AU - Anita N. Boing AU - René Lutter AU - Diana Wouters AU - Gerard J. van Mierlo AU - Sacha S. Zeerleder AU - Elisabeth H. Bel AU - Cornelis van't Veer AU - Alex F. de Vos AU - Jaring S. van der Zee AU - Tom van der Poll Y1 - 2015/09/17 UR - http://erj.ersjournals.com/content/early/2015/09/17/13993003.00459-2015.abstract N2 - 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 ER -