Premature collagen fibril formation, fibroblast-mast cell interactions and mast cell-mediated phagocytosis of collagen in keloids

Abstract

Keloids are benign hyper-proliferative growths of fibrous tissue, where increased fibroblast activity results in abnormal collagen deposition. Excessive inflammation is a characteristic feature of keloids but little is known about the underlying ultrastructural features of keloids related to collagen processing, fibril and fibre formation, the interaction between fibroblasts and associated collagen fibres and mast cells. In this study, the ultrastructure of the dermis of keloid patients was evaluated using light and transmission electron microscopy techniques. Abnormal intracellular premature collagen fibril formation was observed. Phagocytosis of collagen fibrils by mast cells was a common ultrastructural feature of keloid tissue as was a close or direct association between fibroblasts and mast cells. Based on these findings and recent advances in knowledge related to collagen synthesis, fibril formation and processing we hypothesise that keloid formation is primary due to abnormal collagen synthesis where the consequent accumulation of collagen fibres causes increased mast cell recruitment and collagen phagocytosis. Subsequent release of mast cell derived mediators then promotes further collagen synthesis. The observation of early formation in keloid tissue of premature insoluble collagen fibrils supports previous studies that enzymes such as procollagen C-proteinase are important early therapeutic targets.