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 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 beta-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.
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA.
E J
EJ
Papadopoulos
D J
DJ
Fitzhugh
C
C
Tkaczyk
A M
AM
Gilfillan
C
C
Sassetti
D D
DD
Metcalfe
S T
ST
Hwang
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion; D015550:Cell Degranulation; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000032:analysis / Q000502:physiology*; D002633:Chemotaxis; D005260:Female; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D018121:Receptors, Cytokine / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics; D012867:Skin / Q000166:cytology*
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV