Recruitment of CD16+ monocytes into synovial tissues is mediated by fractalkine and CX3CR1 in rheumatoid arthritis patients.
CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood, have been implicated in several inflammatory diseases, including rheumatoid arthritis (RA). Fractalkine (FKN, CX3CL1), a member of the CX3 C subfamily, is induced by pro-inflammatory cytokines, while a receptor for FKN, CX3CR1, is capable of mediating both leukocyte migration and firm adhesion. Here, we investigated the role of FKN and CX3CR1 in activation of CD16+ monocytes and their recruitment into synovial tissues in RA patients. High levels of soluble FKN were detected in the synovial fluid and sera of RA patients. Circulating CD16+ monocytes showed a higher level of CX3CR1 expression than CD16- monocytes in both RA patients and healthy subjects. High level expression of CX3CR1 was also seen in CD16+ monocytes localized to the lining layer in RA synovial tissue. In the in vitro culture experiments, IL-10 induced CX3CR1 expression on the surface of monocytes, and TNFalpha induced membrane-bound FKN as well as soluble FKN expression in synovial fibroblasts. Moreover, soluble FKN was capable of inducing IL-1beta and IL-6 by activated monocytes. These results suggest that FKN might preferentially mediate migration and recruitment of CD16+ monocytes, and might contribute to synovial tissue inflammation.
Yano
Ryusuke
R
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Yamamura
Masahiro
M
Sunahori
Katsue
K
Takasugi
Kouji
K
Yamana
Jiro
J
Kawashima
Masanori
M
Makino
Hirofumi
H
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D000073883:CX3C Chemokine Receptor 1; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010003:Osteoarthritis / Q000097:blood / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D019707:Receptors, Chemokine; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10