The axonal repellent, Slit2, inhibits directional migration of circulating neutrophils
| Autor: | Yves Durocher, Lisa A. Robinson, Min Rui Crow, Chun Xiang Sun, Ming Yan, Yi-Wei Huang, Michael Glogauer, Guang Ying Liu, Ilya Mukovozov, Soumitra Tole, Marco A. O. Magalhaes |
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| Rok vydání: | 2009 |
| Předmět: |
Cell type
Neutrophils Chemokine CXCL2 Immunology Complement C5a Nerve Tissue Proteins Inflammation CDC42 Peritonitis Biology Mice In vivo medicine Animals Humans Immunology and Allergy Receptors Immunologic cdc42 GTP-Binding Protein Receptor Kinase Chemotaxis Interleukin-8 Cell Polarity Cell Biology Slit rac GTP-Binding Proteins Cell biology Enzyme Activation N-Formylmethionine Leucyl-Phenylalanine Disease Models Animal Gene Expression Regulation Intercellular Signaling Peptides and Proteins medicine.symptom |
| Zdroj: | Journal of Leukocyte Biology. 86:1403-1415 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | Slit2, a potentially powerful anti-inflammatory agent, inhibits polarization and chemotaxis, but not random movement, of primary neutrophils towards diverse chemoattractants, in vitro and in vivo. In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals are provided by many different chemotactic molecules, such that blockade of one may not prevent neutrophil recruitment effectively. The Slit family of secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows that by inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit migration of other cell types toward a variety of chemotactic factors in vitro and in vivo. The role of Slit2 in inflammation, however, has been largely unexplored. We isolated primary neutrophils from human peripheral blood and mouse bone marrow and detected Robo-1 expression. Using video-microscopic live cell tracking, we found that Slit2 selectively impaired directional migration but not random movement of neutrophils toward fMLP. Slit2 also inhibited neutrophil migration toward other chemoattractants, namely C5a and IL-8. Slit2 inhibited neutrophil chemotaxis by preventing chemoattractant-induced actin barbed end formation and cell polarization. Slit2 mediated these effects by suppressing inducible activation of Cdc42 and Rac2 but did not impair activation of other major kinase pathways involved in neutrophil migration. We further tested the effects of Slit2 in vivo using mouse models of peritoneal inflammation induced by sodium periodate, C5a, and MIP-2. In all instances, Slit2 reduced neutrophil recruitment effectively (P |
| Databáze: | OpenAIRE |
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