Eosinophil cationic protein alters pulmonary surfactant structure and function in asthma

• 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.

Nyckelord

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

MEDICINE

MEDICIN

Publikations- och innehållstyp

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