Matrix Metalloproteinase-9 Affects Three-Dimensional Collagen Gel Contraction

Abstract

remodeling. Recent studies have implicated the Th2 cytokines interleukin (IL)-4 and IL-13 in airway hyperresponsiveness and COPD.Macrophages stimulated with IL-4 and/or IL-13 are classified as alternatively activated macrophages in contrast to IFN–stimulated classically activated macrophages. In COPD, there is often a combined phenotype of emphysema and airway hyperresponsiveness, with small airway peribronchial fibrosis. Therefore, the purpose of this study was to explore the hypothesis that macrophages in the lung interstitium and airways of patients with COPD display an alternatively activated phenotype, whereas those in the alveolar spaces display the classically activated phenotype. Serial lung sections of human patients with COPD and normal control subjects were immunohistochemically stained for CD68 (a macrophage marker), arginase I and chitinase-like 3 protein (YMV2) (markers of alternatively activated macrophages), and inducible nitric oxide synthase (iNOS; classically activated macrophage marker). In COPD, lung alveolar macrophages stained positive for both CD68 and iNOS, whereas interstitial and peribronchial CD68 macrophages stained positive for both arginase I and YMV2. Normal lung sections had minimal alveolar and interstitial macrophages, with no iNOS-, YMV2, or arginase I–positive cells. Thus, in COPD, lung interstitial and peribronchial macrophages display an alternatively activated phenotype in contrast to alveolar macrophages, which display a classically activated phenotype.