Monocytic origin of fibrosis. In vitro transformation of HLA-DR monocytes into neo-fibroblasts: inhibitory effect of all-trans retinoic acid on this process.
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.
Labat
M L
ML
Laboratoire de Physiopathologie Osseuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Bringuier
A F
AF
Arys-Philippart
C
C
Arys
A
A
Wellens
F
F
D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000009:adverse effects; D005347:Fibroblasts / Q000473:pathology; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D066298:In Vitro Techniques; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000276:immunology / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*
D006684:HLA-DR Antigens; D014212:Tretinoin; D016572:Cyclosporine