Active Remodeling in Idiopathic Interstitial Pneumonias (IIPs): Evaluation of Collagens Types XII and XIV

Eleni G. Tzortzaki ^1*, Anastassios V. Koutsopoulos ¹, Konstantina I. Dambaki ¹, Irini Lambiri ¹, Maria Plataki ¹, Marion K. Gordon ¹, Donald R. Gerecke ¹ and Nikolaos M. Siafakas ¹

¹ 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)

^* To whom correspondence should be addressed. E-mail: tzortzaki{at}med.uoc.gr.

Submitted on September 13, 2005
Accepted on 18 January 2006

	Abstract

FACIT collagens XII and XIV act as organizers of lung collagen fibrils and assist in the maintenance of uniform fibril size and spatial arrangements. To explore the above hypothesis in the human pulmonary fibrotic process, 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 normal control subjects. Immunostaining for collagens XII and XIV was carried out in formalin-fixed, paraffin-embedded lung tissue sections. In addition, picrosirius red histochemical staining was carried out to identify the amount of Collagen I expression and transmission electron microcopy was performed to evaluate fibril diameter. In normal human lung, collagens XII and XIV showed intense staining in perivascular and subpleural connective tissue. In COP/OP collagens XII and XIV showed intense staining in perivascular connective tissue, in thickened alveolar septae and in subpleural areas. In IPF/UIP patients, collagens XII and XIV were expressed in perivascular connective tissue, in areas of established fibrosis and in areas of subpleural thickening. Only collagen XII and not collagen XIV was expressed in granulation tissue plugs in COP/OP and in fibroblastic foci in IPF/UIP tissue samples. Picrosirius red histochemical staining exhibited overexpression of collagen type I in fibrotic areas. Electron micrographs revealed obvious fibril diameter alteration and fusion in the same areas FACIT collagens XII and XIV are expressed in normal and fibrotic human lung. However, 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.

Key Words: pulmonary fibrosis, interstitial pneumonia, FACITs, cryptogenic organizing pneumonia

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