Immunolocalization of collagen and collagen-binding heat shock protein 47 in fibrotic lung diseases

Pulmonary fibrosis resulting from increased accumulation of various extrace llular matrices is a prominent feature in chronic progressive lung diseases . Heat shock protein 47 (HSP47) is a collagen-binding stress protein known to have a specific role in the intracellular processing of procollagen mole cules as a collagen-specific molecular chaperone in various organs. Possibl e involvement, however, of HSP47 in relation to increased deposition of col lagens in fibrotic lung diseases is not yet known. In this study, we invest igated the expression of HSP47 in various pulmonary fibrotic diseases. Form alin-fixed, paraffin-embedded lung sections from 17 autopsies of patients w ith various pulmonary fibrotic diseases, e.g., organizing pneumonia, inters titial pneumonia, idiopathic pulmonary fibrosis, and diffuse alveolar damag e, were stained with monoclonal antibodies for alpha-smooth muscle actin, v imentin, CD68, Type III collagen, and HSP47, The extent of staining was gra ded semiquantitatively, Five control lung sections were also simultaneously studied. The fibrotic lung sections, in comparision with the control secti ons, had more interstitial cells positive for alpha-smooth muscle actin and fibroblasts positive for vimentin; we also saw increased infiltration of C DG8-positive macrophages, For HSP47, in comparison with the control lung se ctions, markedly increased immunostaining was always noted in the fibrotic lung sections in association with increased accumulation of Type III collag en in the fibrotic masses. By double immunostaining, colocalization of coll agens and HSP47 was noted in the regions of pulmonary fibrosis, and HSP47-e xpressing cells were found to be mainly alpha-smooth muscle actin-positive interstitial cells. From the above observations, we concluded that overexpr ession of HSP47 might play an important role in the excessive assembly/synt hesis of collagens and could thereby contribute to the fibrosis found in pu lmonary fibrotic lung diseases.