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1 Research Centre Borstel, Borstel and 2 Grosshansdorf Hospital, Centre for Pneumology and Thoracic Surgery, Grosshansdorf, Germany
CORRESPONDENCE: S. Uhlig, Research Centre Borstel, Division Pulmonary Pharmacology, Parkallee 22, D-23845 Germany. Fax: 49 4537188778. E-mail: suhlig@fz-borstel.de
Keywords: asthma, immunoglobulin E, leukotrienes, small airways, thromboxane
Received: April 3, 2002
Accepted February 12, 2003
This study was supported by the Deutsche Forschungsgemeinschaft grant DFG Uh 88/3-1 to S. Uhlig.
To study the role of small airways in the early allergic response (EAR), the method of human precision-cut lung slices (PCLS) was developed and used to examine the bronchoconstriction elicited by passive sensitisation and allergen provocation.
Viable human PCLS of 250-µm thickness containing airways <1.5 mm in outer diameter were prepared from lung lobes obtained from lung resection and taken into culture. According to the low release of lactate dehydrogenase and the constant ciliary beat frequency, human PCLS were viable for at least 3 days.
Following overnight passive sensitisation with serum from allergic individuals, administration of grass-pollen extract or activating immunoglobulin E antibody resulted in immediate airway contraction that was quantified by videomicroscopy. The extent of the EAR increased with decreasing airway size (outer airway diameter), with the strongest response occurring in the terminal bronchioles.
Histamine receptor antagonism was ineffective, and leukotriene or thromboxane receptor antagonism attenuated the early allergic response only in some cases. However, simultaneous blockade of leukotriene and thromboxane receptors almost completely prevented the early allergic response in the precision-cut lung slices from all individuals, suggesting such a dual treatment as a potential future asthma therapy.
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