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| Content Provider | Springer Nature Link |
|---|---|
| Author | Grommes, Christian Lee, C. Y. Daniel Wilkinson, Brandy L. Jiang, Qingguang Koenigsknecht Talboo, Jessica L. Varnum, Brian Landreth, Gary E. |
| Copyright Year | 2007 |
| Abstract | Removal of apoptotic cells is an essential process for normal development and tissue maintenance. Importantly, apoptotic cells stimulate their phagocytosis by macrophages while actively suppressing inflammatory responses. Growth arrest specific gene 6 (Gas6) is involved in this process, bridging phosphatidylserine residues on the surface of apoptotic cells to the Axl/Mer family of tyrosine kinases which stimulate phagocytosis. Animals with mutations or loss of these receptors exhibit phenotypes reflective of impaired phagocytosis and a hyperactive immune response. We report that Gas6 induces phagocytosis in microglia through a novel non-classical phagocytic mechanism. Gas6 stimulates a type-II-related phagocytic response, but requires Vav phosphorylation and Rac activation, distinguishing it from the classical type II mechanism. Importantly, Gas6 suppressed lipopolysaccharide-induced expression of the inflammatory molecules IL-1β and iNOS. Gas6 inhibited iNOS expression through suppression of promoter activity. The present data provide direct evidence for the role of Gas6 receptors in mediating an anti-inflammatory response to ligands found on apoptotic cells with the simultaneous stimulation of phagocytosis. These data provide a mechanistic explanation for the phenotype observed in animals lacking Axl/Mer receptors. |
| Starting Page | 130 |
| Ending Page | 140 |
| Page Count | 11 |
| File Format | |
| ISSN | 15571890 |
| Journal | Journal of Neuroimmune Pharmacology |
| Volume Number | 3 |
| Issue Number | 2 |
| e-ISSN | 15571904 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2007-10-10 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Vav iNOS IL-1β Rac Phagocytosis microglia Cell Biology Virology Pharmacology/Toxicology Immunology Neurosciences |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology and Allergy Pharmacology Immunology |
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