Autor: |
Ali MN; Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden. Mohamad.Ali@med.lu.se., Mori M; Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University and Skåne University Hospital, Lund, Sweden., Mertens TCJ; Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX, USA., Siddhuraj P; Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University and Skåne University Hospital, Lund, Sweden., Erjefält JS; Unit of Airway Inflammation, Department of Experimental Medical Sciences, Lund University and Skåne University Hospital, Lund, Sweden., Önnerfjord P; Rheumatology & Molecular Skeletal Biology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden., Hiemstra PS; Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands., Egesten A; Respiratory Medicine & Allergology, Department of Clinical Sciences Lund, Lund University and Skåne University Hospital, Lund, Sweden. |
Abstrakt: |
Osteopontin (OPN) plays a role in inflammation via recruitment of neutrophils and tissue remodeling. In this study, we investigated the distribution of OPN-expressing cells in the airway epithelium of normal lung tissue and that from patients with chronic obstructive pulmonary disease (COPD). OPN was detected on the epithelial cell surface of small airways and in scattered cells within the epithelial cell layer. Staining revealed higher OPN concentrations in tissue showing moderate to severe COPD compared to that in controls. In addition, OPN expression was confined to goblet and club cells, and was absent from ciliated and basal cells as detected via immunohistochemistry. However, OPN expression was up-regulated in submerged basal cells cultures exposed to cigarette smoke (CS) extract. Cell fractioning of air-liquid interface cultures revealed increased OPN production from basal compartment cells compared to that in luminal fraction cells. Furthermore, both constitutive and CS-induced expression of OPN decreased during differentiation. In contrast, cultures stimulated with interleukin (IL)-13 to promote goblet cell hyperplasia showed increased OPN production in response to CS exposure. These results indicate that the cellular composition of the airway epithelium plays an important role in OPN expression and that these levels may reflect disease endotypes in COPD. |