| Research Abstract |
1. Histopathological examination of 6 open biopsy cases with acute exacerbation of idiopathic pulmonary fibrosis revealed fresh or organizing diffuse alveolar damage superimposed on the underlying usual interstitial pneumonia in 5 out of 6 cases. In one case, UIP was confirmed with autopsy material. There was no definite cause of DAD, such as viral infection, and it was suggested that acute exacerbation can occur as a natural course of IPF.
2. Among cases of IPF, those with pathological features of NSIP were studied in addition to CVD-associated cases. Pathologically ; interstitial fibrosis and/or inflammation of temporally homogenous nature were seen in a diffuse or patchy manner, accompanied by lymphoid follicles. NSIP was different from other entities, such as UIP, AIP, DIP, BOOP, but borderline cases existed. Further investigation especially focussing on the aasociation of immunologic abnormality is needed.
3. MMPs and TIMPs are known to be important in remodeling of the extracellula
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r matrix and the imbalance of their activities is thought to result in fibrosis. We investigated the expression of MMPs and TIMPs in various types of interstitial pneumonia to elucidate their possible roles in development and progression of the disease. Thirty eight open/thoracoscopic biopsy cases including 16 with UIP, one with DIP, 7 with AIP, 9 with NSIP, and 5 with BOOP were immunohistochemically double-stained using antibodies to type-TV collagen and to MMPsl, 2,3,9 or TIiMPsl, 2 with avidin-biotin peroxidase method. MMPl was commonly expressed in alveolar macrophages, type-II pneumocytes and bronchiolar epithelial cells in all types of IP.MMPs2,9 were more prevalently expressed in cases with UIP and DIP than in others. In contrast, the expression of MMP3 was significant in AlP and BOOP.TIMPs1,2 were expressed in fibroblasts, as well as type-II pneumocytes and alveolar macrophages in all types of IPs, among which UIP and DIP showed stronger expressions than the others.
4. Expressions of various cytokines (TNFalpha, IL-1, IFNy, IL-6) and growth factors (PDGF, IGF-1, TGFbeta, bFGF) were also studied on the same cases as above. TNFalpha, IL-1, IL-6 and PDGF were expressed in neutrophils, alveolar macrophages, type-II pneumocytes and bronchiolar epithelial cells and bronchial cartilagenous cells. IGF-I was also expressed in neutrophils, lymphocytes, alveolar macrophages, type-II pneumocytes and bronchiolar epithelial cells and bronchial cartilagenous cells. bFGFwas expressed in lymphocytes, type-II pneumocytes and bronchiolar epithelial cells. The expressions of cytokines and growth factors are generally broad and not specific.
5. Our results indicate that MMPs 2,9 and TIMPs1,2 are involved chiefly in the chronic processes, such as UIP and DIP, in contrast to the MMP3 expression in acute or subacute diseases including AIP and BOOP.NSIP showed the intermediate pattern of expressions of MMPs and TIMPs. Less
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