Monocytic origin of fibrosis. In vitro transformation of HLA-DR monocytes into neo-fibroblasts: inhibitory effect of all-trans retinoic acid on this process

Abstract

We report here the spontaneous in vitro transformation of blood monocytes into fibroblasts in a patient who developed pulmonary fibrosis following ciclosporin-mediated immunosuppression, necessitated by heart transplantation. The blood monocytes with this capacity expressed HLA-DR specificity. Monocytes/macrophages were identified by immunofluorescence using monoclonal antibodies against a specific monocyte/macrophage antigen, while the neo-fibroblasts were identified by electron microscopy and immunofluorescence using monoclonal antibodies against a cytoplasmic enzyme specifically involved in the synthesis of collagen. The secretion of collagen was demonstrated using antibodies against collagen. Both the monocytes/macrophages and the neo-fibroblasts express macrophage and fibroblast markers and are able to synthesize collagen. The all-trans retinoic acid derivative (all-trans RA) inhibits this in vitro transformation of HLA-DR monocytes/macrophages into neo-fibroblasts. Therefore, the possible therapeutic role of all-trans RA in controlling the development of fibrosis remains open to investigation. Until now, no efficient therapy is known for fibrotic diseases which are often lethal when affecting the lungs.