Research output: Contribution to journal › Article › Academic › peer-review
Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial. / de Boer, J. Daan; Berger, Marieke; Majoor, Christof J. et al.
In: European respiratory journal, Vol. 46, No. 6, 2015, p. 1636-1644.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial
AU - de Boer, J. Daan
AU - Berger, Marieke
AU - Majoor, Christof J.
AU - Kager, Liesbeth M.
AU - Meijers, Joost C. M.
AU - Terpstra, Sanne
AU - Nieuwland, Rienk
AU - Boing, Anita N.
AU - Lutter, René
AU - Wouters, Diana
AU - van Mierlo, Gerard J.
AU - Zeerleder, Sacha S.
AU - Bel, Elisabeth H.
AU - van't Veer, Cornelis
AU - de Vos, Alex F.
AU - van der Zee, Jaring S.
AU - van der Poll, Tom
PY - 2015
Y1 - 2015
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
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
U2 - 10.1183/13993003.00459-2015
DO - 10.1183/13993003.00459-2015
M3 - Article
C2 - 26381519
VL - 46
SP - 1636
EP - 1644
JO - European respiratory journal
JF - European respiratory journal
SN - 0903-1936
IS - 6
ER -
ID: 2699299