Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease.
J. Nat. Med. 13, 1423-1430 (2007)
Interleukin-8 (IL-8) activates neutrophils via the chemokine receptors CXCR1 and CXCR2. However, the airways of individuals with cystic fibrosis are frequently colonized by bacterial pathogens, despite the presence of large numbers of neutrophils and IL-8. Here we show that IL-8 promotes bacterial killing by neutrophils through CXCR1 but not CXCR2. Unopposed proteolytic activity in the airways of individuals with cystic fibrosis cleaved CXCR1 on neutrophils and disabled their bacterial-killing capacity. These effects were protease concentration-dependent and also occurred to a lesser extent in individuals with chronic obstructive pulmonary disease. Receptor cleavage induced the release of glycosylated CXCR1 fragments that were capable of stimulating IL-8 production in bronchial epithelial cells via Toll-like receptor 2. In vivo inhibition of proteases by inhalation of alpha1-antitrypsin restored CXCR1 expression and improved bacterial killing in individuals with cystic fibrosis. The cleavage of CXCR1, the functional consequences of its cleavage, and the identification of soluble CXCR1 fragments that behave as bioactive components represent a new pathophysiologic mechanism in cystic fibrosis and other chronic lung diseases.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Animals; Cystic Fibrosis/immunology*; Cystic Fibrosis/microbiology*; Glycosylation;Humans; Interleukin-8/metabolism; Lung/microbiology; Mice; Models; biological;Neutrophils/metabolism*; Neutrophils/microbiology; Receptors; Interleukin-8A/metabolism
ISSN (print) / ISBN 1340-3443
Zeitschrift Journal of natural medicines
Quellenangaben Band: 13, Heft: 12, Seiten: 1423-1430
Verlagsort Tokyo [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) CCG Immune Regulation in Childhood (IMI-KIK)