PMID- 11373340
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20220316
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 12
IP  - 6
DP  - 2001 Jun
TI  - Obstructive nephropathy in the mouse: progressive fibrosis correlates with 
      tubulointerstitial chemokine expression and accumulation of CC chemokine receptor 
      2- and 5-positive leukocytes.
PG  - 1173-1187
LID - 10.1681/ASN.V1261173 [doi]
AB  - The infiltration of leukocytes plays a major role in mediating tubulointerstitial 
      inflammation and fibrosis in chronic renal disease. CC chemokines participate in 
      leukocyte migration and infiltration into inflamed renal tissue. Because CC 
      chemokine-directed leukocyte migration is mediated by target cell expression of a 
      group of CC chemokine receptors, this study examined the expression of CC 
      chemokines and their receptors during initiation of tubulointerstitial fibrosis 
      after unilateral ureteral obstruction in C57BL/6 mice. Obstructed kidneys 
      developed hydronephrosis, tubular cell damage, interstitial inflammation, and 
      fibrosis. From days 2 to 10, a progressive interstitial influx of F4/80+ 
      macrophages and CD3+ lymphocytes occurred (macrophages, 4-fold; lymphocytes, 
      20-fold at day 10, compared with contralateral control kidneys). In parallel, the 
      number of activated fibroblast-specific protein 1+ fibroblasts and interstitial 
      collagen IV accumulation increased from days 2 to 10. The mRNA expression of CC 
      chemokines (predominantly monocyte chemoattractant protein-1 [MCP-1]/CCL2, 
      RANTES/CCL5) and their receptors CCR1, CCR2, CCR5 increased progressively from 
      days 2 to 10. By in situ hybridization, a prominent interstitial mRNA expression 
      of MCP-1 and RANTES and their receptors CCR2 and CCR5 localized to interstitial 
      mononuclear cell infiltrates. MCP-1 and RANTES expression was also seen in 
      tubular epithelial cells. Fluorescence-activated cell sorter analysis of 
      single-cell suspensions from obstructed kidneys revealed a prominent expression 
      of CCR2 and CCR5 by infiltrating macrophages, whereas most lymphocytes expressed 
      CCR5 only. These data demonstrate an increased expression of MCP-1/CCL2 and 
      RANTES/CCL5 at sites of tubulointerstitial damage and progressive fibrosis during 
      unilateral ureteral obstruction that correlates with simultaneous accumulation of 
      interstitial macrophages and T lymphocytes expressing the respective surface 
      receptors CCR2 and CCR5. The chemokine receptor-mediated leukocyte influx into 
      the tubulointerstitium could offer a new potential target for therapeutic 
      intervention in progressive renal tubulointerstitial fibrosis.
FAU - Vielhauer, Volker
AU  - Vielhauer V
AD  - Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-University, 
      Munich, Germany.
FAU - Anders, Hans-Joachim
AU  - Anders HJ
AD  - Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-University, 
      Munich, Germany.
FAU - Mack, Matthias
AU  - Mack M
AD  - Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-University, 
      Munich, Germany.
FAU - Cihak, Josef
AU  - Cihak J
AD  - Department of Animal Physiology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Strutz, Frank
AU  - Strutz F
AD  - Department of Nephrology and Rheumatology, University of Gottingen, Gottingen, 
      Germany.
FAU - Stangassinger, Manfred
AU  - Stangassinger M
AD  - Department of Animal Physiology, Ludwig-Maximilians-University, Munich, Germany.
FAU - Luckow, Bruno
AU  - Luckow B
AD  - Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-University, 
      Munich, Germany.
FAU - Grone, Hermann-Josef
AU  - Grone HJ
AD  - Department of Cellular and Molecular Pathology, German Cancer Research Center, 
      Heidelberg, Germany.
FAU - Schlondorff, Detlef
AU  - Schlondorff D
AD  - Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-University, 
      Munich, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Chemokines, CC)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - Animals
MH  - Chemokines, CC/*metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Fibrosis
MH  - Flow Cytometry
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization
MH  - Leukocytes
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nephritis, Interstitial/*metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Receptors, Chemokine/*metabolism
MH  - Ureteral Obstruction/*metabolism/pathology
EDAT- 2001/05/25 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/05/25 10:00
PHST- 2001/05/25 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/05/25 10:00 [entrez]
AID - 12/6/1173 [pii]
AID - 10.1681/ASN.V1261173 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2001 Jun;12(6):1173-1187. doi: 10.1681/ASN.V1261173.