Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin

Mast cells (MC) are anatomically located near nerves acid blood vessels in skin and the gastrointestinal tract and tend to localize within certain cut aneous tumors such as neurofibromas, However, the molecular mechanisms by w hich MC home to these sites are not well characterized. Fractalkine (FK) is a membrane-bound CX3C chemokine that displays constitutive expression in d endritic cells as well as in non-hematopoietic tissues including mammalian brain. Here we show that FK is constitutively expressed by skin endothelial cells, dermal dendrocytes and cells within neurofibromas. By reverse trans cription-PCR, FK receptor, CX3CR1, is expressed by cultured murine bone mar row-derived MC (BMMC) of both connective tissue and mucosal phenotypes. Non -activated human dermal MC isolated from neonatal foreskin similarly demons trated CX3CR1 expression. In chemotaxis assays, FK attracted MC with maxima l migration occurring between 25-125 ng/ml. BMMC were not stimulated to rel ease proinflammatory mediators in the presence of FK as measured by granule -associated beta-hexosaminidase release, Thus, CX3CR1 is expressed by MC an d effectively mediates chemotaxis without inducing degranulation. We propos e that the constitutive expression of FK on certain cells in the skin may b e a factor in the tissue-specific homing of MC.