El manto dela tierra

Immunology 2000 99 435±439

Mast cells enhance contraction of three-dimensional collagen lattices by ®broblasts by cell±cell interaction: role of stem cell factor/c-kit
T. YAMAMOTO, K. HARTMANN,B. ECKES & T. KRIEG Department of Dermatology, University of Cologne, Cologne, Japan

SUMMARY Reorganization of the extracellular matrix is important in many biological and pathophysiologicalprocesses, including tissue remodelling, wound healing, or cancer metastasis. The ability of cultured ®broblasts to reorganize and contract three-dimensional type I collagen gels is regarded as an in vitromodel for this process. In tissue ®brosis, complex interactions among ®broblasts, in¯ammatory cells and the extracellular matrix are taking place. Mast cells have often been discussed to play a role inseveral ®brotic conditions including scleroderma, scar formation, or wound healing. In this study, we examined the effects of mast cells on contraction of collagen lattices. The results demonstratethat co-culture of dermal ®broblasts with a human mast cell line (HMC-1) signi®cantly enhanced contraction of the three-dimensional collagen lattices, whereas mast cells alone failed to contract thegel. Addition of culture supernatants of mast cells did not enhance the speed of gel contraction, indicating the importance of cell±cell contact. Morphological analysis showed that mast cells wereincorporated into the lattices. Histological examination also demonstrated that within the lattices, mast cells were localized in close contact to, or attached to, ®broblasts. As ®broblasts and mast cellsare known to attach via stem cell factor (SCF)/c-kit interaction when co-cultured in monolayers, we also examined the effect of antibodies against SCF and c-kit in this system. Addition of bothantibodies inhibited gel contraction up to 70%. In contrast, antibodies against interleukin-4 (IL-4) and IL-4 receptor did not affect gel contraction. These results indicate that mast cells enhance...