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Active Remodeling in Idiopathic Interstitial Pneumonias: Evaluation of Collagen Types XII and XIV

Eleni G. Tzortzaki, Anastassios V. Koutsopoulos, Konstantina I. Dambaki, Irini Lambiri, Maria Plataki, Marion K. Gordon, Donald R. Gerecke and Nikolaos M. Siafakas

Department of Thoracic Medicine (EGT,IL,MP,NMS) and Department of Pathology (AVK,KID), University General Hospital Medical School, University of Crete, Crete, Greece, and Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (MKG,DRG)

Correspondence to: Eleni G. Tzortzaki, MD, PhD, Department of Thoracic Medicine, University General Hospital Medical School, University of Crete, Heraklion 71110, Crete, Greece. E-mail: tzortzaki{at}med.uoc.gr

Fibril-associated collagens with interrupted triple helices (FACITs) XII and XIV act as fibril organizers and assist in the maintenance of uniform fibril size. We investigated the spatial expression patterns of collagens XII and XIV in cryptogenic organizing pneumonia (COP)/organizing pneumonia (OP) and in idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) and compared them to normal human lung. Study subjects included 10 patients with COP/OP, 10 patients with IPF/UIP, and 8 control subjects. Immunostaining for collagens XII and XIV was carried out in paraffin-embedded human lung tissue sections. Picrosirius red histochemical staining for collagen I expression and electron microcopy to evaluate fibril diameter were also performed. In normal lung, collagens XII and XIV were expressed in perivascular and subpleural connective tissue. In COP/OP, both collagens showed intense staining in perivascular connective tissue, thickened alveolar septae, and subpleural areas. In IPF/UIP, XII and XIV were expressed in perivascular connective tissue, in areas of established fibrosis, and in areas of subpleural thickening. Only collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblastic foci in IPF/UIP. Collagen type I was overexpressed in fibrotic areas. Electron micrographs revealed obvious fibril diameter alteration and fusion in the same areas. FACITs XII and XIV are expressed in normal and fibrotic lung. Unlike collagen XIV, collagen XII was expressed in granulation tissue plugs in COP/OP and in fibroblast foci in IPF/UIP. This may suggest a possible distinct role for both collagens in the modulation of the extracellular matrix during the onset of fibrotic process. (J Histochem Cytochem 54:693–700, 2006)

Key Words: pulmonary fibrosis • interstitial pneumonia • fibril-associated collagens with interrupted triple helices • cryptogenic organizing pneumonia

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