Epithelial cell‐derived human β‐defensin‐2 acts as a chemotaxin for mast cells through a pertussis toxin‐sensitive and phospholipase C‐dependent pathway

Abstract

Mast cells are known to accumulate at the sites of inflammation in response to chemoattractants generated in the local milieu. Since human β‐defensin‐2 (hBD‐2) is generated in several epithelial tissues where mast cells are present and because we have recently reported that this human antibacterial peptide induces mast cell degranulation, we thus hypothesized that hBD‐2 could be a mast cell chemotaxin. Here we report that hBD‐2 directly and specifically induces mast cell migration with an optimal concentration of 3 µg/ml. Checkerboard analysis showed that the migration was more chemotactic rather than chemokinetic. Moreover, Scatchard analysis using ¹²⁵I‐labeled hBD‐2 revealed that mast cells have at least two classes of receptors, high‐ and low‐affinity receptors, for this peptide. Moreover, the competitive binding assay suggested that hBD‐2 is unlikely to utilize CCR6, a functional receptor for hBD‐2‐mediated dendritic and T cell migration, on mast cells. In addition, treatment of mast cells with G protein inhibitor, pertussis toxin, and phospholipase C inhibitor, U‐73122, abolished the cell chemotaxis in response to hBD‐2, indicating that the G protein–phospholipase C signaling pathway is involved in hBD‐2‐induced mast cell activation. Thus, we suggest that hBD‐2, which was originally believed to be involved in innate host defense, may participate in the recruitment of mast cells to inflammation foci.