Deficiency in collagen and fibronectin phagocytosis by human buccal mucosafibroblasts in vitro as a possible mechanism for oral submucous fibrosis

Oral submucous fibrosis (OSF), a chronic oral mucosal condition commonly fo und in south Asians, is a disorder characterized by a quantitative as well as a qualitative alteration of collagen deposition within the subepithelial layer of the oral mucosa. Since degradation of collagen by fibroblast phag ocytosis is an important pathway for physiological remodelling of soft conn ective tissues, we have investigated phagocytosis of collagen- and fibronec tin-coated latex beads by fibroblast cultures with an in vitro model system . Coated fluorescent latex beads were incubated with human oral mucosa fibr oblasts and the fluorescence associated with internalized beads was measure d by flow cytometry. Cells from normal tissues that had been incubated with beads for 16 h contained a mean of 75% collagen phagocytic cells and 70% f ibronectin phagocytic cells; however, about 15% and 10% of phagocytic cells individually contained more than twice the mean number of beads per cell. In contrast, cells from OSF tissues exhibited a 40% reduction of the propor tions of collagen phagocytic cells (mean = 35%) and a 48% decrease of the p roportions of fibronectin phagocytic cells (mean = 22%), none of the cells having a high number of beads as compared to normal fibroblasts. OSF lesion s appear to contain fibroblasts with marked deficiencies in collagen and fi bronectin phagocytosis. To investigate if inhibition of phagocytosis could be demonstrated in vitro, normal fibroblast cultures were incubated with ar eca nut alkaloids (arecoline, arecaidine). The cultures had a dose-dependen t reduction in the proportions of phagocytic cells. On the other hand, cort icosteroid used in the treatment of OSF exhibited a dose-dependent enhancem ent in the proportion of phagocytic cells. Therefore, our hypothesis for OS F, although oversimplified, is that betel nut alkaloids (arecoline, arecaid ine) inhibit fibroblast phagocytosis and this provides a mechanism for the development of OSF. The benefit of a local intralesional injection of corti costeroid is also possibly, at least in part, through an enhancement of fib roblast collagen phagocytosis.