Our data suggested that beta1-integrin shedding produced by repetitive allergen challenges in guinea-pigs was associated with collagen deposition in SER of bronchi and bronchioles, along with inflammatory cells infiltration and AI-AHR development.

No abstract

Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

Barometric plethysmography for unrestrained animals is a non-invasive method that allows repetitive measurements of pulmonary function, but habituation of the conscious animal to this technique has not been explored. Respiratory frequency (f R ) and 'enhanced pause' (P enh ) were measured by barometric plethysmography for a period of 8 h in guinea-pigs. Compared with basal values, during the first hour of recording a progressive increase in P enh (up to 25-50%) and a corresponding decrease in f R were recorded, followed by a relative plateau in each for up to 8 h. These changes were avoided by a 30-min pretreatment with propranolol and L-NAME (nitric oxide synthase inhibitor), with P enh values as high as this plateau phase since the beginning of recording. Atropine, salbutamol or budesonide did not modify the progressive increment in P enh . We concluded that catecholamines and nitric oxide are released when guinea-pigs are introduced into the plethysmographic chamber, leading to initial low P enh values. These mediators probably diminish owing to habituation of the animal to the new environment, with an apparent progressive increment in P enh . These spontaneous changes in P enh and f R must be taken into account during barometric plethysmography in order to avoid misinterpretation of the results.

Asthma is a chronic, heterogeneous and variable disease in which airways inflammation, transient obstruction and hyperresponsiveness are the major features of the illness (