Human Skin-Derived Mast Cells Spontaneously Secrete Several Angiogenesis-Related Factors

Mast cells are classically recognized as cells that cause IgE-mediated allergic reactions. However, their ability to store and secrete vascular endothelial growth factor (VEGF) suggests a role in vascular development and tumorigenesis. The current study sought to determine if other angiogenesis-related factors, in addition to VEGF, were also secreted by human tissue-derived mast cells. Using proteome array analysis and ELISA, we found that human skin-derived mast cells spontaneously secrete CXCL16, DPPIV, Endothelin-1, GM-CSF, IL-8, MCP-1, Pentraxin 3, Serpin E1, Serpin F1, TIMP-1, Thrombospondin-1, and uPA. We identified three groups based on their dependency for stem cell factor (SCF), which is required for mast cell survival: Endothelin-1, GM-CSF, IL-8, MCP-1, and VEGF (dependent); Pentraxin 3, Serpin E1, Serpin F1, TIMP-1, and Thrombospondin-1 (partly dependent); and CXCL16, DPPIV, and uPA (independent). Crosslinking of FcεRI with multivalent antigen enhanced the secretion of GM-CSF, Serpin E1, IL-8, and VEGF, and induced Amphiregulin and MMP-8 expression. Interestingly, FcεRI signals inhibited the spontaneous secretion of CXCL16, Endothelin-1, Serpin F1, Thrombospondin-1, MCP-1 and Pentraxin-3. Furthermore, IL-6, which we previously showed could induce VEGF, significantly enhanced MCP-1 secretion. Overall, this study identified several angiogenesis-related proteins that, in addition to VEGF, are spontaneously secreted at high concentrations from human skin-derived mast cells. These findings provide further evidence supporting an intrinsic role for mast cells in blood vessel formation.