PMID- 19889873
OWN - NLM
STAT- MEDLINE
DCOM- 20100603
LR  - 20171116
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 25
IP  - 3
DP  - 2010 Mar
TI  - The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin 
      nephrosis.
PG  - 717-30
LID - 10.1093/ndt/gfp569 [doi]
AB  - BACKGROUND: Blockade of CD40-CD40 ligand (CD154) interactions protects against 
      renal injury in adriamycin nephropathy (AN) in immunocompetent mice. To 
      investigate whether this protection relied on adaptive or cognate immunity, we 
      tested the effect of CD40-CD154 blockade in severe combined immunodeficient 
      (SCID) mice. METHODS: SCID mice were divided into three groups: normal, AN + 
      hamster IgG (ADR+IgG group) and AN + anti-CD154 antibody (MR1) (ADR+MR1 group). 
      AN was induced by tail vein injection of 5.2 mg/kg of adriamycin (ADR). Hamster 
      IgG (control Ab) or MR1 was administered intraperitoneally on days 5, 7, 9 and 11 
      after ADR injection. Histological and functional data were collected 4 weeks 
      after ADR injection. In vitro experiments tested the effect of soluble and 
      cell-bound CD154 co-cultured with CD40-expressing cells [macrophages, mesangial 
      cells and renal tubular epithelial cells (RTEC)]. RESULTS: All experimental 
      animals developed nephropathy. Compared to the ADR+IgG group, ADR+MR1 animals had 
      significantly less histological injury (glomerulosclerosis and tubular atrophy) 
      and functional injury (creatinine clearance). Kidneys of ADR+MR1 animals had 
      significantly less macrophage infiltration than those of ADR+IgG animals. 
      Interestingly, expression of CD40 and CD41 (a platelet-specific marker) was 
      significantly less in ADR+MR1 animals compared to ADR+IgG animals. In vitro, 
      CD154 blockade significantly attenuated upregulation of CCL2 gene expression by 
      RTEC stimulated by activated macrophage-conditioned medium. In contrast, 
      platelet-induced upregulation of macrophage and mesangial cell proinflammatory 
      cytokine gene expression were not CD154-dependent. CONCLUSION: CD40-CD154 
      blockade has a significant innate renoprotective effect in ADR nephrosis. This is 
      potentially due to inhibition of macrophage-derived soluble CD154.
FAU - Lee, Vincent W S
AU  - Lee VW
AD  - Centre for Transplant and Renal Research, Westmead Millennium Institute, 
      University of Sydney at Westmead Hospital, NSW, Australia. 
      vincent_lee@wmi.usyd.edu.au
FAU - Qin, Xiaohong
AU  - Qin X
FAU - Wang, Yiping
AU  - Wang Y
FAU - Zheng, Guoping
AU  - Zheng G
FAU - Wang, Ya
AU  - Wang Y
FAU - Wang, Ying
AU  - Wang Y
FAU - Ince, Jon
AU  - Ince J
FAU - Tan, Thian K
AU  - Tan TK
FAU - Kairaitis, Lukas K
AU  - Kairaitis LK
FAU - Alexander, Stephen I
AU  - Alexander SI
FAU - Harris, David C H
AU  - Harris DC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091104
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (CD40 Antigens)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antibodies, Anti-Idiotypic/pharmacology
MH  - CD40 Antigens/antagonists & inhibitors/*physiology
MH  - CD40 Ligand/antagonists & inhibitors/*physiology
MH  - Chemokine CCL2/physiology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Doxorubicin/*adverse effects
MH  - Epithelial Cells/drug effects/immunology/pathology
MH  - Immunity, Innate/*physiology
MH  - Kidney Tubules/drug effects/immunology/pathology
MH  - Macrophages/metabolism/pathology
MH  - Mesangial Cells/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, SCID
MH  - Nephrosis/*chemically induced/pathology/*physiopathology
MH  - Signal Transduction/*physiology
EDAT- 2009/11/06 06:00
MHDA- 2010/06/04 06:00
CRDT- 2009/11/06 06:00
PHST- 2009/11/06 06:00 [entrez]
PHST- 2009/11/06 06:00 [pubmed]
PHST- 2010/06/04 06:00 [medline]
AID - gfp569 [pii]
AID - 10.1093/ndt/gfp569 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2010 Mar;25(3):717-30. doi: 10.1093/ndt/gfp569. Epub 
      2009 Nov 4.