Remodeling of the lung in bleomycin-induced pulmonary fibrosis in the rat. An immunohistochemical study of laminin, type IV collagen, and fibronectin

Abstract

Intratracheal injection of bleomycin in rats results in the development of patchy pulmonary fibrosis. We investigated events associated with remodeling of lung structure by light and electron microscopic immunolocalization of fibronectin, laminin, and type IV collagen. Animals were studied from 2 to 60 days after injection of bleomycin. In the acute phase of injury, staining of fibronectin was prominent in fibrinous exudates, whereas during healing it was mainly associated with the surface of fibroblasts. The early accumulation of fibronectin in alveolar exudates is probably the result of leakage of plasma. During the reparative phase, fibronectin may be synthesized locally since it is selectively associated with the fibroblast surface. Staining with antibodies to type IV collagen and laminin identified the basal lamina and also helped to define the tissue boundaries despite the presence of intense exudation. It highlighted two processes in the acutely injured lung that lead to abnormal lung architecture: collapse of alveoli and invasion of air spaces by fibroblasts. In some healed lesions at 20 and 60 days, the immunostaining still outlined atelectatic lung. Electron microscopy of these lesions showed collagenous synechiae between approximated alveolar walls. We suggest that alveolar collapse and intraalveolar fibrosis in areas of collapse play an important role in bleomycin-induced pulmonary fibrosis and probably other types of fibrosis. They readily explain the loss of lung volume and compliance characteristic of fibrotic lung.