PMID- 12472771
OWN - NLM
STAT- MEDLINE
DCOM- 20040302
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 63
IP  - 1
DP  - 2003 Jan
TI  - Adoptive transfer studies demonstrate that macrophages can induce proteinuria and 
      mesangial cell proliferation.
PG  - 83-95
AB  - BACKGROUND: Glomerular macrophage accumulation is a feature of proliferative 
      human and experimental glomerulonephritis. However, our understanding of the role 
      of macrophages in the induction of renal injury is based upon indirect evidence 
      from depletion studies, most of which lack specificity for this cell type. 
      Therefore, an adoptive transfer approach was used to directly assess the 
      potential of macrophages to induce renal injury. METHODS: Accelerated 
      anti-glomerular basement membrane (anti-GBM) disease was induced in rats by 
      immunization with sheep IgG (day -5), followed by administration of sheep 
      anti-rat GBM serum (day 0), with animals killed on day 2. To facilitate the 
      adoptive transfer studies, immunized animals were made leukopenic by 
      cyclophosphamide (CyPh) given on day -2. Bone marrow-derived (BM) or NR8383 
      macrophages were transferred by tail vein injection 24 hours after injection of 
      anti-GBM serum, with animals killed 3 or 24 hours after transfer. RESULTS: 
      Pretreatment with CyPh prevented glomerular leukocyte accumulation and completely 
      inhibited proteinuria, glomerular cell proliferation and hypercellularity in 
      accelerated anti-GBM disease. Adoptive transfer led to significant glomerular 
      accumulation of BM or NR8383 macrophages within 3 hours of injection, and this 
      was still evident 24 hours later. Adoptive transfer of BM or NR8383 macrophages 
      induced proteinuria (63 +/- 16 BM vs. 5 +/- 2 mg/24 h CyPh control; P < 0.001), 
      glomerular cell proliferation (5.1 +/- 1.2 BM vs. 0.5 +/- 0.1 PCNA+ cells/gcs 
      CyPh; P < 0.001) and glomerular hypercellularity (51.2 +/- 2.0 BM vs. 41.9 +/- 
      0.9 nuclei/gcs CyPh; P < 0.001). The degree of renal injury correlated with the 
      number of transferred glomerular macrophages. Two-color immunostaining 
      demonstrated that most glomerular proliferative cell nuclear antigen+ (PCNA+) 
      proliferating cells were OX-7+ mesangial cells. CyPh treatment did not prevent 
      up-regulation of glomerular intercellular adhesion molecule-1 (ICAM-1) and 
      vascular cell adhesion molecule (VCAM-1) expression or an increase in urinary 
      monocyte chemoattractant protein-1 (MCP-1) excretion. CONCLUSION: This study 
      provides the first direct evidence that macrophages can induce renal injury in 
      terms of proteinuria and mesangial cell proliferation.
FAU - Ikezumi, Yohei
AU  - Ikezumi Y
AD  - Department of Nephrology and Monash University, Clayton, Victoria, Australia.
FAU - Hurst, Lynette A
AU  - Hurst LA
FAU - Masaki, Takao
AU  - Masaki T
FAU - Atkins, Robert C
AU  - Atkins RC
FAU - Nikolic-Paterson, David J
AU  - Nikolic-Paterson DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunosuppressive Agents)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - *Adoptive Transfer
MH  - Animals
MH  - Anti-Glomerular Basement Membrane Disease/drug therapy/immunology/*pathology
MH  - Bone Marrow Cells
MH  - Cell Division/immunology
MH  - Cell Line
MH  - Cyclophosphamide/pharmacology
MH  - Disease Models, Animal
MH  - Glomerular Mesangium/immunology/*pathology
MH  - Immunoglobulin G/pharmacology
MH  - Immunosuppressive Agents/pharmacology
MH  - Macrophages, Alveolar/*pathology
MH  - Proteinuria/drug therapy/immunology/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2002/12/11 04:00
MHDA- 2004/03/03 05:00
CRDT- 2002/12/11 04:00
PHST- 2002/12/11 04:00 [pubmed]
PHST- 2004/03/03 05:00 [medline]
PHST- 2002/12/11 04:00 [entrez]
AID - S0085-2538(15)48847-7 [pii]
AID - 10.1046/j.1523-1755.2003.00717.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Jan;63(1):83-95. doi: 10.1046/j.1523-1755.2003.00717.x.