Effect of PEEP on induced constriction is enhanced in decorin-deficient mice

Abstract

Decorin ( Dcn), a small leucine-rich proteoglycan, is present in the extracellular matrix of the airways and lung tissues, contributes to lung mechanical properties, and its deposition is altered in asthma. The effect of Dcn deficiency on airway parenchymal interdependence was examined during induced bronchoconstriction. Studies were performed in C57Bl/6 mice in which the Dcn gene was disrupted by targeted deletion ( Dcn−/−) and in wild-type controls ( Dcn+/+). Mice were mechanically ventilated, and respiratory system impedance was measured during in vivo ventilation at positive end-expiratory pressure (PEEP) = 2 and 10 cmH20, before and after aerosol delivery of methacholine (MCh). Length vs. tension curves in isolated tracheal rings were measured in vitro. Dcn distribution in +/+ mice airways was characterized by immunofluorescence; differences in collagen structure in Dcn+/+ and Dcn−/− mouse lungs was examined by electron microscopy. MCh caused similar increases in airway resistance (Raw) and tissue elastance (H) in Dcn+/+ and Dcn−/− mice. During MCh-induced constriction, increasing PEEP caused a decrease in Raw that was greater in Dcn−/− mice and a decrease in H in Dcn−/− mice only. Tracheal ring compliance was greater in Dcn −/− mice. Imaging studies showed that Dcn was deposited primarily in the airway adventitial layer in Dcn+/+ mice; in Dcn−/− mice, collagen had an irregular appearance, especially in the lung periphery. These results show that lack of Dcn alters the normal interaction between airways and lung parenchyma; in asthma, changes in Dcn could potentially contribute to abnormal airway physiology.