Cellular localization of fractalkine at sites of inflammation: antigen-presenting cells in psoriasis express high levels of fractalkine

Background Chemokines play a key role in cell trafficking at sites of infla mmation. The fractalkine CX3C chemokine is unique in several aspects. Fract alkine is expressed on activated endothelial cells and exists in two forms, either membrane anchored or in a soluble form. The soluble form is a poten t chemotactic agent for T cells/monocytes and the anchored form functions a s an adhesion molecule. In view of these specific functions fractalkine is capable of controlling the key regulatory mechanisms of cell trafficking at sites of inflammation. Objectives Little is known about the significance of this important molecul e in inflammatory diseases. We undertook this study to elucidate the role o f fractalkine in inflammatory diseases of the skin. Methods We used a polyclonal antifractalkine antibody (immunoperoxidase and immunofluorescence stainings) in cryosections obtained from tissues of nor mal skin and that of selected cutaneous inflammatory diseases (psoriasis, l ichen planus, eczema). Results Increased expression of fractalkine was observed in the dermal bloo d vessels of lichen planus, eczema and psoriasis tissues. The most striking finding was that the dermal dendrocytes in the papillary dermis of psorias is tissues expressed high levels of fractalkine. Compared with 186.64 +/- 5 1.69 fractalkine positive dermal dendrocytes per mm(2) of the upper dermis of psoriatic tissue, the number of positive cells in lichen planus, eczema, and normal skin were 17.29 +/- 12.50, 12.50 +/- 6.75 and 5.93 +/- 3.53, re spectively. We also performed double label immunofluorescence staining with nerve growth factor receptor (NGF-R) antibody and fractalkine antibody. NG F-R-positive terminal cutaneous nerves were in close contact with the fract alkine-positive dermal dendrocytes in psoriatic lesions. Conclusions The results of this study confirm that fractalkine is upregulat ed at sites of inflammation. Thus, it is likely that this molecule plays a key part in cell trafficking. An increased expression of fractalkine at the dermal papillae provides a plausible explanation for the migration and acc umulation of T cells at these sites in psoriasis. Earlier studies have repo rted an increased number of dermal dendrocytes in psoriatic tissue; however , the functional role of these cells in the pathogenesis of psoriasis is la rgely unknown. Expression of fractalkine on the surface of dermal dendrocyt es suggests an active role for these cells in localization and activation o f lesional T cells.