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PMID: 9104823 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis.

The Journal of experimental medicine ·Vol. 185 ·No. 7 ·1997-04-07 ·Pages 1371-80

Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, Gutierrez-Ramos JC

Abstract

The involvement of chemokines in inflammation is well established, but their functional role in disease progression, and particularly in the development of fibrosis, is not yet understood. To investigate the functional role that the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis we have developed and characterized a murine model for this syndrome. Significant increases in T-lymphocytes and macrophages were observed within glomeruli and interstitium, paralleled by an induction of mRNA expression of MCP-1 and RANTES, early after disease initiation. Blocking the function of MCP-1 or RANTES resulted in significant decreases in proteinuria as well as in numbers of infiltrating leukocytes, indicating that both MCP-1 and RANTES (regulated upon activation in normal T cells expressed and secreted) play an important role in the inflammatory phase of crescentic nephritis. In addition, neutralization of MCP-1 resulted in a dramatic decrease in both glomerular crescent formation and deposition of type I collagen. These results highlight a novel role for MCP-1 in crescent formation and development of interstitial fibrosis, and indicate that in addition to recruiting inflammatory cells this chemokine is critically involved in irreversible tissue damage.

MeSH Terms
Animals Chemokine CCL2 Chemokine CCL5 Collagen/biosynthesis,genetics Disease Models, Animal Disease Progression Fibrosis/etiology Glomerulonephritis/etiology Immunohistochemistry Kidney/pathology Mice Proteinuria RNA, Messenger/analysis
Chemicals
Chemokine CCL2 Chemokine CCL5 RNA, Messenger Collagen
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lloyd C M
Department of Medicine, Boston University Medical Center, Massachusetts 02118, USA.
Minto A W
Dorf M E
Proudfoot A
Wells T N
Salant D J
Gutierrez-Ramos J C
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.7.1371
Published
1997-04-07
Pages
1371-80
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196251
Subset
IM
Grants
Wellcome Trust · 087618 · United Kingdom
NIDDK NIH HHS · DK30932 · United States
NHLBI NIH HHS · HL 148675-02 · United States
NCPDCID CDC HHS · CICYT PB93-0317 · United States
External Links
PubMed source DOI: 10.1084/jem.185.7.1371 PMC Full Text View journal details
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