title: FITC-induced murine pulmonary inflammation: CC10 up-regulation and concurrent Shh expression.
abstract: We describe an immunohistochemical study of the acute and chronic effects of fluorescein isothiocyanate (FITC) on Sonic hedgehog (Shh) expression and Clara cell secretory protein (CC10) up-regulation in murine lung. FITC was dissolved in PBS and instilled non-surgically into adult mouse lungs via the trachea. During the acute phase (120h) of the FITC response, CC10 staining within Clara cells increased markedly but the protein did not leak into the tissue spaces or the airways, and no fibrosis was apparent. An immune response was evident, characterised by infiltrating T and B lymphocytes. There was no concomitant expression of Shh. During the chronic phase (6 months post-instillation), significant tissue degeneration was observed in the airways. There was moderate to severe fibrosis in the lung fields that stained positively for FITC and significant inflammatory cell infiltrate was observed. Shh was expressed, and CC10 showed multiple sites of diffuse staining consistent with release from Clara cells into alveolar air spaces. PBS controls showed no fibrosis after 6 months, but there was positive Shh staining below the airway epithelia and minimal extracellular CC10 staining. The results may throw some light on the role of CC10 in pulmonary inflammation. The relationship of Shh expression and CC10 leakage to lung damage and repair is discussed.
authors.affiliation: Centre for Inflammation Research, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, Scotland, UK. carolyn.fisher@ed.ac.uk
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Fisher
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Ahmad
authors.forename: Paul M
authors.initials: PM
authors.lastname: Fitch
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
authors.forename: Sarah E M
authors.initials: SE
authors.lastname: Howie
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000633:toxicity*; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains / Q000196:embryology; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis*; D014598:Uteroglobin / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C556390:Scgb1a1 protein, mouse; C465570:Shh protein, mouse; D015534:Trans-Activators; D014598:Uteroglobin; D016650:Fluorescein-5-isothiocyanate