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Glomerular expression of C-C chemokines in different types of human crescentic glomerulonephritis.

Abstract Crescentic glomerulonephritis (CGN) presents a rapidly progressive glomerulonephritis clinically, in which macrophages play a crucial role in the pathogenesis. However, the precise molecular mechanism of macrophage recruitment and activation has not been fully elucidated. C-C chemokines, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha and beta (MIP-1alpha and MIP-1beta), are major chemoattractants for macrophages. We attempted to study the expression of C-C chemokines and their correlation with CD68-positive macrophages in crescentic glomeruli to investigate further their possible roles in crescent formation and progression to fibrosis in different types of human CGN.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title nephrology, dialysis, transplantation : official publication of the european dialysis and transplant association - european renal association
Publication Year Start




PMID- 12897090
OWN - NLM
STAT- MEDLINE
DA  - 20030804
DCOM- 20031117
LR  - 20071115
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 18
IP  - 8
DP  - 2003 Aug
TI  - Glomerular expression of C-C chemokines in different types of human crescentic
      glomerulonephritis.
PG  - 1526-34
AB  - BACKGROUND: Crescentic glomerulonephritis (CGN) presents a rapidly progressive
      glomerulonephritis clinically, in which macrophages play a crucial role in the
      pathogenesis. However, the precise molecular mechanism of macrophage recruitment 
      and activation has not been fully elucidated. C-C chemokines, monocyte
      chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha and 
      beta (MIP-1alpha and MIP-1beta), are major chemoattractants for macrophages. We
      attempted to study the expression of C-C chemokines and their correlation with
      CD68-positive macrophages in crescentic glomeruli to investigate further their
      possible roles in crescent formation and progression to fibrosis in different
      types of human CGN. METHODS: The expression of MCP-1, MIP-1alpha, MIP-1beta and
      CD68 was detected in glomeruli with different forms of crescents (cellular,
      fibrocellular and fibrous crescents) by immunohistochemistry in serial sections
      of renal biopsies taken from 32 patients with biopsy-proven CGN including eight
      patients with anti-glomerular basement membrane (GBM) disease (type I CGN), 12
      patients with immune complex-mediated CGN (type II CGN) and another 12 patients
      with pauci-immune CGN (type III CGN) enrolled in this study. Eight normal human
      kidneys were obtained from cadaveric renal transplant donors whose kidneys were
      technically unsuitable for transplantation, serving as controls. RESULTS: MCP-1, 
      MIP-1alpha, MIP-1beta and CD68 were undetectable in glomeruli of normal kidney.
      In crescentic biopsies, MCP-1, MIP-1alpha, MIP-1beta and CD68 were detected in
      fibrocellular crescents and were even more prominent in cellular crescents, but
      were undetectable in fibrous crescents. Using consecutive sections for staining, 
      it was demonstrated that a high proportion of infiltrating CD68-positive
      macrophages, mainly localized to the area of the expression of chemokines, were
      MCP-1, MIP-1alpha and MIP-1beta positive in crescents. Chemokines were expressed 
      mainly by CD68-positive macrophages and parietal epithelial cells in crescents.
      The number of MCP-1- and MIP-1alpha-positive cells in glomeruli with cellular
      crescents was positively correlated with the number of CD68-positive cells (r =
      0.568 and 0.749, respectively, both P < 0.01). The number of MCP-1- and
      MIP-1alpha-positive cells and the incidence of Bowman's capsule rupture in
      glomeruli of patients with type I CGN were higher than those of type II and type 
      III CGN. CONCLUSIONS: These observations suggest that the expressed C-C
      chemokines, MCP-1, MIP-1alpha and MIP-1beta, may mediate the inflammatory process
      of crescent formation and progression to fibrosis. The strong correlation of
      MCP-1 and MIP-1alpha with infiltrating macrophages within glomeruli with cellular
      crescents suggested that these chemokines might be of particular importance for
      macrophage recruitment to this site. MCP-1 and MIP-1alpha were correlated to type
      I CGN with its more severe inflammatory course and worse prognosis. The variance 
      of glomerular expression of C-C chemokines may contribute to the difference in
      histopathological features and prognosis in these three types of CGN.
FAU - Liu, Zhi-Hong
AU  - Liu ZH
AD  - Research Institute of Nephrology, Nanjing University School of Medicine, Jinling 
      Hospital, Nanjing, PR China. [email protected]
FAU - Chen, Shu-Fen
AU  - Chen SF
FAU - Zhou, Hong
AU  - Zhou H
FAU - Chen, Hui-Ping
AU  - Chen HP
FAU - Li, Lei-Shi
AU  - Li LS
LA  - eng
PT  - Journal Article
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 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokines, CC)
RN  - 0 (Macrophage Inflammatory Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL3
MH  - Chemokine CCL4
MH  - Chemokines, CC/*metabolism
MH  - Child
MH  - Disease Progression
MH  - Female
MH  - Glomerulonephritis/*metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunohistochemistry
MH  - Kidney Glomerulus/*metabolism
MH  - Macrophage Inflammatory Proteins/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Middle Aged
EDAT- 2003/08/05 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/05 05:00
PST - ppublish
SO  - Nephrol Dial Transplant. 2003 Aug;18(8):1526-34.

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