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      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

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          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.

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          Most cited references 37

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            Transforming growth factor beta in tissue fibrosis.

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              Relationship between renal function and histological changes found in renal-biopsy specimens from patients with persistent glomerular nephritis.

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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                7 April 1997
                : 185
                : 7
                : 1371-1380
                Affiliations
                From the [* ]Department of Medicine, Boston University Medical Center, Boston, Massachusetts 02118; []The Center for Blood Research, Incorporated and Department of Genetics and the [§ ]Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115; []Glaxo Institute for Molecular Biology, Geneva, CH1228 Switzerland; and []Millennium Pharmaceuticals Inc., Cambridge Massachusets 02139
                Author notes

                Address correspondence to J.C. Gutierrez-Ramos, Millennium Pharmaceuticals Inc., 640 Memorial Drive, Cambridge, MA 02139. Any queries regarding the murine model of crescentic nephritis should be directed to Dr. D. Salant, Renal Section, Department of Medicine, 88 East Newton St., Boston, MA 02118.

                Article
                2196251
                9104823
                Categories
                Article

                Medicine

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