Mast cells enhance contraction of three-dimensional collagen lattices by fibroblasts by cell-cell interaction: role of stem cell factor/c-kit

Reorganization of the extracellular matrix is important in many biological and pathophysiological processes, including tissue remodelling, wound heali ng, or cancer metastasis. The ability of cultured fibroblasts to reorganize and contract three-dimensional type I collagen gels is regarded as an in v itro model for this process. In tissue fibrosis, complex interactions among fibroblasts, inflammatory cells and the extracellular matrix are taking pl ace. Mast cells have often been discussed to play a role in several fibroti c conditions including scleroderma, scar formation, or wound healing. In th is study, we examined the effects of mast cells on contraction of collagen lattices. The results demonstrate that co-culture of dermal fibroblasts wit h a human mast cell line (HMC-1) significantly enhanced contraction of the three-dimensional collagen lattices, whereas mast cells alone failed to con tract the gel. Addition of culture supernatants of mast cells did not enhan ce the speed of gel contraction, indicating the importance of cell-cell con tact. Morphological analysis showed that mast cells were incorporated into the lattices. Histological examination also demonstrated that within the la ttices, mast cells were localized in close contact to, or attached to, fibr oblasts. As fibroblasts and mast cells are known to attach via stem cell fa ctor (SCF)/c-kit interaction when co-cultured in monolayers, we also examin ed the effect of antibodies against SCF and c-kit in this system. Addition of both antibodies inhibited gel contraction up to 70%. In contrast, antibo dies against interleukin-4 (IL-4) and IL-4 receptor did not affect gel cont raction. These results indicate that mast cells enhance fibroblast-mediated contraction of collagen lattices via direct cell-cell contact, mediated in part by SCF/c-kit interactions.