A Monoclonal Antibody to the Carboxyterminal Domain of Procollagen Type I Visualizes Collagen-synthesizing Fibroblasts Detection of an Altered Fibroblast Phenotype in Lungs of Patients with Pulmonary Fibrosis

Excessive collagen deposition plays a critical role in the devel-opment of fibrosis, and early or active fibrosis may be more susceptible to therapeutic intervention than later stages of scar-ring. However, at present there is no simple method for assessing the collagen-synthesizing and secreting activity of fibroblasts in human tissues. Type I procollagen carboxyterminal domains are proteolytically removed during collagen secretion. Thus, anti-bodies to these domains should stain fibroblasts synthesizing type I collagen but not extracellular collagen fibrils which could mask the signal from the cells. We developed and characterized a monoclonal antibody (Anti-pC) specific for the carboxyterminal propeptide of type I procollagen. To determine the relationship between Anti-pC staining and collagen synthesis, we stained em-bryonic and adult chicken tendon. Embryonic chick tendon fi-broblasts actively synthesizing type I collagen stained heavily with Anti-pC, while quiescent adult tendon fibroblasts did not stain with Anti-pC. Wounded adult tendons developed fibroblasts that stained with Anti-pC at the wound site. Thus, Anti-pC spe-cifically visualized fibroblasts actively synthesizing collagen. Lung biopsies from patients with fibrotic lung disease were stained with Anti-pC. Interstitial and intraalveolar fibroblasts in biopsies from patients with active fibrosis stained intensely with Anti-pC, while normal human lung was unstained. The ab-sence of staining in normal lung supports the hypothesis that fibrosis is associated with an altered collagen-synthesizing phe-notype of tissue fibroblasts. Anti-pC may provide a useful clinical tool for assessing fibrogenic activity at sites of tissue injury