prolyl-glycyl-proline and Asthma

It is anticipated that bioactive fragments of the extracellular matrix (matrikines) can influence the development and progression of chronic diseases. The enzyme leukotriene A

Topics: Airway Remodeling; Airway Resistance; Animals; Asthma; Bronchi; Cell Count; Disease Models, Animal; Epithelial Cells; Epoxide Hydrolases; Extracellular Matrix; Humans; Hypersensitivity; Inflammation; Inflammation Mediators; Mice, Inbred C57BL; Mucus; Neutrophils; Oligopeptides; Proline; Pyroglyphidae; Respiratory Hypersensitivity; Sputum; T-Lymphocytes, Helper-Inducer

The consequences on lung function and inflammation of alterations in the extracellular matrix affecting the peripheral airway wall in asthma are largely unknown. We hypothesized that remodeling of collagen and elastic fibers in the peripheral airway wall leads to airway obstruction and contributes to neutrophilic airway inflammation. Animals used were six heaves-affected horses and five controls. Large peripheral lung biopsies were obtained from horses with heaves in clinical remission (Baseline) and during disease exacerbation and from age-matched controls. The area of collagen and elastic fiber content in the lamina propria was measured by histological staining techniques and corrected for airway size. Collagen type 1 and type 3 content was further assessed from additional horses after postmortem lung samples by immunohistochemistry. The collagen breakdown products proline-glycine-proline (PGP) and N-acetylated-PGP (N-α-PGP) were also measured in bronchoalveolar lavage fluids (BALF) by mass spectrometry. Compared with controls, heaves-affected horses had an increase in collagen (P = 0.05) and elastic fiber contents (P = 0.04) at baseline. Collagen types 1 and 3 content was also significantly increased in diseased horses (P = 0.015) when both collagen types were combined. No further change in collagen content was observed after a 30-day antigenic challenge. Airway collagen at baseline was positively correlated with pulmonary resistance in asthmatic horses (r(2) = 0.78, P = 0.03) and elastic fiber content was positively associated with pulmonary elastance in controls (r(2) = 0.95, P = 0.02). No difference between groups was appreciated in PGP and N-α-PGP peptides in BALF. Increased airway wall collagen and elastic fiber content may contribute to residual obstruction in the asthmatic airways.

Topics: Airway Obstruction; Animals; Asthma; Bronchoalveolar Lavage Fluid; Collagen Type I; Collagen Type III; Elastic Tissue; Horse Diseases; Horses; Inflammation; Lung; Neutrophils; Oligopeptides; Proline; Prospective Studies