Higher Metabolic Activity in Fibroblastic Foci of UIP Than in Buds of Fibrosis in Intra-Alveolar Buds in COP/BOOP.
Osamu Matsubara, Keisuke Kobayashi, Sohei Yamamoto, Ryoko Kikuchi, Kenichi Iwaya, Yukio Nakatani, Richard L Kradin, Eugene J Mark. National Defense Medical College, Tokorozawa, Saitama, Japan; Chiba University, Japan; Massachusetts General Hospital and Harvard Medical School, Boston
Background: Fibroblastic foci in profusion contribute to irreversible fibrosis in UIP. Polypoid granulation tissue plugging small airways (intra-alveolar bud) is one of the pathologic characteristics of COP/ BOOP. UIP and COP/BOOP are clinically distinct. The ubiquitin gene is expressed in eukaryotic cells and plays a role in the regulation of cell cycle, apoptosis and signal transmission. We compared the expression of ubiquitin, polyubiquitin, ubiquitinized proteins, various growth factors and an apoptotic marker in UIP and COP/BOOP.
Design: Immunostaining for ubiquitin (P4D1 mouse mAb, Cell Signaling Technology), transforming growth factor (TGF) beta-1, connective tissue growth factor (CTGF), proliferating cell nuclear antigen(PCNA)and Ki-67 was carried out in paraffin-embedded sections of lung from 10 thoracoscopic biopsies with COP/BOOP and 10 biopsies with UIP using a standard indirect avidin-biotin horseradish peroxidase method with various antigen retrievals. Apoptotic DNA strand break by nick end-labeling technique (TUNEL) was also examined.
Results: Ubiquitin and ubiquitinized proteins were expressed in the cytoplasm and nucleus of bronchial and bronchiolar epithelial cells but not in pneumocytes in normal controls. It was expressed in regenerative type 2 pneumocytes and alveolar macrophages both in UIP and COP/BOOP. Ubiquitin and ubiquitinized proteins were expressed strongly in myofibroblasts in fibroblastic foci but faintly in intra-alveolar buds. Growth factors were expressed strongly in fibroblastic foci, regenerating type 2 pneumocytes and bronchiolar epithelial cells in UIP but faintly in intra-alveolar buds and seldom in pneumocytes adjacent to the lesions in COP/BOOP. PCNA-positive pneumocytes, bronchiolar epithelial cells and fibroblasts were frequent in UIP but not in COP/BOOP. TUNEL signals were seldom seen either in fibroblastic foci or in intra-alveolar buds.
Conclusions: Expression of ubiquitin, ubiquitinized proteins and growth factors in the fibroblastic foci in UIP suggest up-regulation of cell cycles and the ubiquitin proteasome system. Thus, there is higher metabolic activity in the fibroblastic foci in UIP when compared to the intra-alveolar buds in COP/BOOP. The difference may contribute to the different natural history of the two diseases.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 259, Wednesday Morning