Activated protein C inhibits neutrophil migration in allergic asthma: a randomised trial.
Eur Respir J
; 46(6): 1636-44, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26381519
ABSTRACT
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 (24â
µg·kg(-1)·h(-1); n=12) or placebo (n=12) for 11â
h. 4â
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 8â
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hipersensibilidade Respiratória
/
Asma
/
Extratos de Tecidos
/
Proteína C
/
Movimento Celular
/
Dermatophagoides pteronyssinus
/
Neutrófilos
Tipo de estudo:
Clinical_trials
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Eur Respir J
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Holanda