Crucial role of CD8-positive lymphocytes in glomerular expression of ICAM-1 and cytokines in crescentic glomerulonephritis of WKY rats.
CD8-positive lymphocytes (CD8+ lym) and ICAM-1/LFA-1 interaction have been implicated in the glomerular accumulation of monocytes/macrophages (Mo/Mphi) and crescent formation in antiglomerular basement membrane (anti-GBM) glomerulonephritis of WKY rats. In the present study, the role of CD8+ lym in the expression of ICAM-1 and inflammatory cytokines as well as in the accumulation of Mo/Mphi in the glomeruli was examined by RNase protection assay and immunofluorescence microscopy. ICAM-1 expression was apparent at 1 h and markedly enhanced at day 3 in glomeruli after an anti-GBM Ab injection in parallel with glomerular accumulation of Mo/Mphi. Expression of mRNA for IL-1beta, TNF-alpha, and IFN-gamma, known to enhance ICAM-1 expression, and MIP-1alpha, MIP-1beta, and MCP-1, known to activate leukocyte integrins or to act as chemokines, were also induced in the glomeruli at a mRNA level in a profile similar to that of ICAM-1 expression. By depleting the CD8+ lym in the circulation, the increased glomerular expression of ICAM-1 and the cytokines, except IL-1beta, and the Mo/Mphi accumulation were suppressed, indicating a crucial role of CD8+ lym in the accumulation of Mo/Mphi through stimulation of ICAM-1 and induction of cytokines.
Fujinaka
H
H
Department of Pathology, Institute of Nephrology, Niigata University School of Medicine, Japan.
Yamamoto
T
T
Feng
L
L
Kawasaki
K
K
Yaoita
E
E
Hirose
S
S
Goto
S
S
Wilson
C B
CB
Uchiyama
M
M
Kihara
I
I
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005921:Glomerulonephritis / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D007958:Leukocyte Count; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY / Q000276:immunology*
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1