Fractalkine expression and CD16+ monocyte accumulation in glomerular lesions: association with their severity and diversity in lupus models.
Fractalkine (Fkn) is expressed on injured endothelial cells and is a membrane-bound chemokine that attracts cells expressing its receptor, CX3CR1, including CD16(+) monocytes (CD16(+) Mos). To clarify the role played by Fkn in the development of glomerular lesions in lupus nephritis, we examined Fkn expression and CD16(+) Mo accumulation induced in experimental C.B-17/Inc-scid/scid (SCID) lupus model mice by injection of IgG(3)-producing hybridoma clones obtained from MRL/lpr mice. Glomerular Fkn expression and accumulation of CD16(+) Mos were semiquantitatively evaluated using laser capture microdissection and real-time PCR. Injection of the 2B11.3 and 7B6.8 clones induced formation of glomerular proliferative and wire-loop lesions, respectively. Immunohistological analysis of the localization of Fkn and CD16(+) Mos revealed that Fkn expression and CD16(+) Mo accumulation were markedly elevated in glomerular lesions induced by 2B11.3, whereas no elevation was detected in those induced by 7B6.8. In addition, to examine the contribution of glomerular Fkn to the development of proliferative lesions, L cells producing an Fkn antagonist (Fkn-AT) were transplanted into SCID mice exhibiting proliferative lupus nephritis (DPLN) induced by 2B11.3. Notably, transplantation of the Fkn-AT-producing cells was functionally and histologically protective against this DPLN. Taken together, our findings suggest that Fkn and CD16(+) Mo accumulation are partially associated with the severity and diversity of histology of lupus nephritis.
Nakatani
Kimihiko
K
First Dept. of Internal Medicine, Nara Medical Univ., 840, Shijo-cho, Kashihara, Nara, 634-8522, Japan. nkimihik@naramed-u.ac.jp
Yoshimoto
Shuhei
S
Iwano
Masayuki
M
Asai
Osamu
O
Samejima
Ken-ichi
K
Sakan
Hirokazu
H
Terada
Miho
M
Hasegawa
Hitoshi
H
Nose
Masato
M
Saito
Yoshihiko
Y
D000818:Animals; D049109:Cell Proliferation; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation; D006801:Humans; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D007739:L Cells; D008181:Lupus Nephritis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D019463:Mice, Inbred MRL lpr; D016513:Mice, SCID; D042282:Microdissection; D009000:Monocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D012720:Severity of Illness Index; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D012333:RNA, Messenger; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha