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

Fractalkine (FKN) induces activation and adhesion of leukocytes expressing its receptor, CX(3)CR1. FKN is released from the cell surface through proteolytic cleavage as soluble FKN (sFKN). We sought to assess FKN and CX(3)CR1 expression in the skin, serum sFKN levels, and CX(3)CR1 expression on blood leukocytes in patients with atopic dermatitis (AD). FKN and CX(3)CR1 expression in the skin was examined immunohistochemically. mRNA expression of FKN, thymus and activation-regulated chemokine, and macrophage-derived chemokine in the skin was assessed by means of real-time RT-PCR. Serum sFKN levels were assessed by using ELISA. Blood leukocytes were stained for CX(3)CR1 by means of flow cytometric analysis. FKN was strongly expressed on endothelial cells in skin lesions of patients with AD and psoriasis but not in normal skin. FKN mRNA levels in AD lesional skin increased to a similar extent to thymus and activation-regulated chemokine and macrophage-derived chemokine mRNA levels. CX(3)CR1-expressing cells in the affected skin of patients with AD or psoriasis increased compared with those in normal skin. Serum sFKN levels were increased in patients with AD but not in patients with psoriasis relative to levels in healthy control subjects. Serum sFKN levels were associated with the disease severity and decreased with the improvement of skin lesions in patients with AD. CX(3)CR1(+) cell frequencies and CX(3)CR1 expression levels were decreased in CD8(+) T cells, monocytes, and natural killer cells from patients with AD, but this was not observed in patients with psoriasis. These results suggest that through functions in both membrane-bound and soluble forms, FKN plays an important role in the trafficking of CX(3)CR1(+) leukocytes during the inflammation caused by AD.

Echigo T ，Hasegawa M ，Shimada Y ，Takehara K ，Sato S ... -  《JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY》

Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis.

Hasegawa M ，Sato S ，Echigo T ，Hamaguchi Y ，Yasui M ，Takehara K ... -  《-》

Fractalkine, a novel chemokine in rheumatoid arthritis and in rat adjuvant-induced arthritis.

To examine the expression of the novel CX3C chemokine fractalkine (Fkn) and its receptor (CX3CR1) in rheumatoid arthritis (RA) and rat adjuvant-induced arthritis (AIA), a model of RA. Immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), and chemotaxis assays were used. In rat AIA, synovial tissue (ST) macrophages, fibroblasts, endothelial cells, and dendritic cells were Fkn immunopositive, whereas lymphocytes did not significantly express Fkn. Significant staining for CX3CR1 was found in ST macrophages, fibroblasts, and dendritic cells, whereas only a small percentage of endothelial cells stained for CX3CR1 in rat AIA. We immunolocalized Fkn to RA ST macrophages, fibroblasts, endothelial cells, and dendritic cells. We also found intense ST macrophage and dendritic cell staining for CX3CR1 in RA ST. Flow cytometry analysis of RA synovial fluid (SF) and peripheral blood revealed a greater percentage of monocytes expressing Fkn and CX3CR1 compared with T cells. By ELISA, we found significantly elevated soluble Fkn (sFkn) levels in RA SF compared with SF from patients with osteoarthritis or other forms of arthritis. By RT-PCR, we found enhanced expression of Fkn and CX3CR1 mRNA on day 18 in rat AIA, a time of pronounced inflammation in the rat joint. Soluble Fkn-depleted RA SF showed significantly decreased chemotactic activity for monocytes compared with sham-depleted RA SF. These results indicate that Fkn and its receptor are both expressed in RA and in rat AIA, and that sFkn is up-regulated in RA SF. Furthermore, our data suggest a new role for Fkn in monocyte chemotaxis in the inflamed RA joint.

Ruth JH ，Volin MV ，Haines GK 3rd ，Woodruff DC ，Katschke KJ Jr ，Woods JM ，Park CC ，Morel JC ，Koch AE ... -  《ARTHRITIS AND RHEUMATISM》

Increased serum levels of soluble fractalkine (CX3CL1) correlate with disease activity in rheumatoid vasculitis.

Matsunawa M ，Isozaki T ，Odai T ，Yajima N ，Takeuchi HT ，Negishi M ，Ide H ，Adachi M ，Kasama T ... -  《ARTHRITIS AND RHEUMATISM》

Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations.

Yajima N ，Kasama T ，Isozaki T ，Odai T ，Matsunawa M ，Negishi M ，Ide H ，Kameoka Y ，Hirohata S ，Adachi M ... -  《ARTHRITIS AND RHEUMATISM》