uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Show others and affiliations
2004 (English)In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 113, no 3, 496-502 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Impaired surfactant function has been demonstrated in patients with asthma. Inhibitory proteins originating from plasma or inflammatory mediators are good candidates to contribute to this dysfunction. Eosinophils are potent effector cells in asthma, which, on activation, release inflammatory mediators, especially reactive granula proteins such as eosinophil cationic protein (ECP).

OBJECTIVE: Because the potential role of ECP in the inhibition of surfactant function is not known, we tested the hypothesis of whether ECP levels in bronchoalveolar lavage fluid (BALF) of patients with asthma after segmental allergen provocation correlate to surfactant dysfunction. Furthermore, we tested the effect of purified ECP on surfactant function and structure in vitro.

METHODS: Surfactant isolated from BALF of asthmatic patients was assessed for biophysical function with the Pulsating Bubble Surfactometer and the Capillary Surfactometer and correlated to ECP levels. Purified ECP and plasma proteins at various concentrations were incubated with natural surfactant. Surfactant function was studied with the Capillary Surfactometer, and surfactant structure was determined by electron microscopy.

RESULTS: ECP is elevated in BALF from patients with asthma after allergen challenge compared with baseline. ECP levels after allergen challenge correlate well to surfactant dysfunction. In vitro, ECP induces a concentration-dependent inhibition of surfactant function that can be inhibited by antibodies against ECP. ECP is more potent compared with albumin or fibrinogen. Finally, ECP induces severe ultrastructural changes to surfactant vesicles that are more pronounced than changes induced by either fibrinogen or albumin.

CONCLUSIONS: ECP contributes to surfactant dysfunction in asthma, which in turn could lead to airway obstruction.

Place, publisher, year, edition, pages
2004. Vol. 113, no 3, 496-502 p.
Keyword [en]
Adult, Animals, Asthma/*physiopathology, Blood Proteins/pharmacology/*physiology, Bronchial Provocation Tests, Bronchoalveolar Lavage Fluid/chemistry, Case-Control Studies, Cattle, Eosinophil Granule Proteins, Female, Humans, In Vitro, Male, Microscopy; Electron, Pulmonary Surfactants/*chemistry/*metabolism, Research Support; Non-U.S. Gov't, Ribonucleases/pharmacology/*physiology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-73030DOI: 10.1016/j.jaci.2003.12.008PubMedID: 15007353OAI: oai:DiVA.org:uu-73030DiVA: diva2:100941
Available from: 2005-05-31 Created: 2005-05-31 Last updated: 2010-11-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=15007353&dopt=Citation

Search in DiVA

By author/editor
Venge, Per
By organisation
Department of Medical Sciences
In the same journal
Journal of Allergy and Clinical Immunology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 199 hits
ReferencesLink to record
Permanent link

Direct link