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

Abstract

Mast cells (MC) are anatomically located near nerves and blood vessels in skin and the gastrointestinal tract and tend to localize within certain cutaneous tumors such as neurofibromas. However, the molecular mechanisms by which MC home to these sites are not well characterized. Fractalkine (FK) is a membrane‐bound CX3C chemokine that displays constitutive expression in dendritic 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 transcription‐PCR, FK receptor, CX3CR1, is expressed by cultured murine bone marrow‐derived MC (BMMC) of both connective tissue and mucosal phenotypes. Non‐activated human dermal MC isolated from neonatal foreskin similarly demonstrated CX3CR1 expression. In chemotaxis assays, FK attracted MC with maximal migration occurring between 25 – 125 ng / ml. BMMC were not stimulated to release proinflammatory mediators in the presence of FK as measured by granule‐associated β‐hexosaminidase release. Thus, CX3CR1 is expressed by MC and effectively mediates chemotaxis without inducing degranulation. We propose that the constitutive expression of FK on certain cells in the skin may be a factor in the tissue‐specific homing of MC.

Enhanced Recruitment of CX3CR1+ T Cells by Mucosal Endothelial Cell–Derived Fractalkine in Inflammatory Bowel Disease

“…A significant degree of THP1 cell migration through HIMEC was observed, though to a lesser degree than that induced by MCP-1, the prototypical monocyte chemoattractant 43, 44 . These results indicate that FKN, although displaying features different from those of other classes of chemokines 43,44,61,62 , can also play a traditional chemotactic role in IBD, particularly for CD16+ monocytes 60, 63 .…”

Role of CX3CR1 (Fractalkine Receptor) in Brain Damage and Inflammation Induced by Focal Cerebral Ischemia in Mouse

“…Fractalkine has been shown to serve as a potent chemoattractant for natural killer cells, CD8 + T cells (Imai et al, 1997), and mast cells (Papadopoulos et al, 2000). Neutrophils can be recruited to the brain independently of fractalkine by various substances released under pathologic conditions.…”

Expression of fractalkine and its receptor, CX3CR1, in atopic dermatitis: Possible contribution to skin inflammation

“…FKN is expressed in various organs including skin, tonsils, brain, and kidney 12,[14][15][16] and interacts with its unique receptor, CX 3 CR1, expressed on monocytes, natural killer (NK) cells, and some T cells. FKN and CX 3 CR1 represent a novel type of leukocyte trafficking molecule that regulates both adhesive and chemotactic functions 17 .…”