Modulation of Inflammation by Slit Protein In Vivo in Experimental Crescentic Glomerulonephritis
| Autor: | Suhua Han, Curtis B. Wilson, John Kanellis, Lili Feng, Gustavo Parra, C. Wayne Smith, Richard J. Johnson, Gabriela Garcia, Jane Y. Wu, Yi Rao, Ping Li |
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| Rok vydání: | 2004 |
| Předmět: |
Male
rac1 GTP-Binding Protein Chemokine Blotting Western Down-Regulation Nerve Tissue Proteins Inflammation Biology Rats Inbred WKY Cell Line Pathology and Forensic Medicine Glomerulonephritis Antigens CD In vivo medicine Animals RNA Messenger Chemokine CCL2 Cell chemotaxis Reverse Transcriptase Polymerase Chain Reaction Chemotaxis Flow Cytometry medicine.disease Recombinant Proteins Rats Cell biology Chemotaxis Leukocyte Disease Models Animal Gene Expression Regulation Immunology Leukocytes Mononuclear biology.protein Intercellular Signaling Peptides and Proteins Animal Model medicine.symptom Ex vivo Leukocyte chemotaxis |
| Zdroj: | The American Journal of Pathology. 165:341-352 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)63301-9 |
| Popis: | A basic conservation of cell migration guidance mechanisms in the nervous and immune systems was proposed when Slit, known for its role in axon guidance, was found to inhibit chemokine-induced leukocyte chemotaxis in vitro. These studies examined the role of Slit2 in modulating inflammation in vivo. In a rat model of glomerulonephritis, endogenous glomerular Slit2 expression fell after disease induction, and its inhibition during the early disease period accelerated inflammation. Ex vivo glomerular leukocytes showed decreased chemokine and chemoattractant-induced chemotaxis in response to Slit2, suggesting an anti-inflammatory role for glomerular Slit2. In contrast to the effect of inhibition, glomerulonephritis was ameliorated by systemic Slit2 administration. Slit2 treatment improved disease histologically and also improved renal function when given early in the disease course. Leukocytes harvested from rats receiving Slit2 showed decreased monocyte chemoattractant protein-1 (MCP)-1-mediated migration, consistent with a peripheral Slit2 effect. In keeping with this functional alteration, Slit2-mediated inhibition of RAW264.7 cell chemotaxis was associated with decreased levels of active cdc42 and Rac1, implicating GTPases in leukocyte Slit2 signaling. These findings suggest a role for endogenous Slit2 in the inhibition of chemoattractant-mediated signals, demonstrate a potentially important anti-inflammatory effect for Slit2 in vivo, and provide further evidence for conserved mechanisms guiding the process of migration in distinct cell types. |
| Databáze: | OpenAIRE |
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