Role of mesothelial and submesothelial stromal cells in matrix remodeling following pleural injury

Abstract

The pleural response to injury is a complex and poorly understood multifactorial process that can result in the development of fibrosis or obliteration of the pleural space. Pleural fibroblasts are considered the main source of extracellular matrix but cell culture studies have demonstrated synthesis of matrix components by mesothelial cells. We assessed the mesothelial cell contribution to extracellular matrix during pleural healing using immunohistochemical technique. Paraffin-embedded tissue of 3 normal adult lungs and 7 adults with active pleuritis were studied using monoclonal antibodies to cytokeratin, type IV collagen, vimentin, and type I procollagen (PCI). Normal pleural had a single layer of cytokeratin-positive and PCI-negative mesothelium over a thin, continuous type IV collagen-positive basement membrane and PCI-negative submesothelial stroma. Areas of active pleuritis showed loss of the continuous linear staining with anti-type IV collagen antibody. Coexpression of cytokeratin, vimentin and PCI was identified in spindle and/or cuboidal cells located in the fibrin layer, submesothelial connective tissue layer, or on the pleural surface. These findings suggest that reactive mesothelial cells play an active role in the production of extracellular matrix during pleural injury, and that disruption of the submesothelial basement membrane is a key event in determining subsequent fibrous organization of pleural exudate.