Immunohistochemical study of collagen types in human foetal lung and fibrotic lung disease.

Highly purified type-specific anti-collagen antibodies (prepared in animals to types I, II, III, and IV bovine collagen) were used in an indirect immunofluorescence method for the study of human lung collagen. The tissue localisation of each collagen type, and the apparent type I:III collagen ratio was assessed in normal foetal and adult lung and in fibrotic lung lesions. In the latter, the relationship of the findings to the natural history of the lesion was considered. This method was compared with routine connective tissue stains. The following observations were made. (1) Foetal lung in the canalicular phase of development proved a useful substrate for validating and standardizing the procedure. (2) Collagen fluorescence was more sensitive than connective tissue stains in detecting collagen in foetal tissues and sites of early fibrosis. (3) On the basis of collagen-type fluorescence, two distinctive patterns of fibrosis were recognised. Areas of mature collagen surrounding vessels and bronchi and in established scar tissue, for example in asbestotic pleural plaques, were virtually exclusively type I collagen. By contrast, areas of early active fibrosis like sarcoid nodules and organising pneumonia, which usually contained variable numbers of fibroblasts and chronic inflammatory cells, were characterised by an increased proportion of type III collagen and a greater intensity of both types I and III collagen fluorescence. The possible significance of this change in type III:I collagen ratio is discussed. Determination of the stage of fibrotic lesions by this method might have applications in the prediction of disease progression, and influence management of some conditions.