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Endothelial reticulon-4B (Nogo-B) regulates ICAM-1–mediated leukocyte transmigration and acute inflammation
| Content Provider | Scilit |
|---|---|
| Author | Lorenzo, Annarita Di Manes, Thomas D. Davalos, Alberto Wright, Paulette L. Sessa, William C. |
| Copyright Year | 2011 |
| Description | The reticulon (Rtn) family of proteins are localized primarily to the endoplasmic reticulum (ER) of most cells. The Rtn-4 family, (aka Nogo) consists of 3 splice variants of a common gene called Rtn-4A, Rtn-4B, and Rtn-4C. Recently, we identified the Rtn-4B (Nogo-B) protein in endothelial and smooth muscle cells of the vessel wall, and showed that Nogo-B is a regulator of cell migration in vitro and vascular remodeling and angiogenesis in vivo. However, the role of Nogo-B in inflammation is still largely unknown. In the present study, we use 2 models of inflammation to show that endothelial Nogo-B regulates leukocyte transmigration and intercellular adhesion molecule-1 (ICAM-1)–dependent signaling. Mice lacking Nogo-A/B have a marked reduction in neutrophil and monocyte recruitment to sites of inflammation, while Nogo-A/B−/− mice engrafted with wild-type (WT) bone marrow still exhibit impaired inflammation compared with WT mice engrafted with Nogo-A/B−/− bone marrow, arguing for a critical role of host Nogo in this response. Using human leukocytes and endothelial cells, we show mechanistically that the silencing of Nogo-B with small interfering RNA (siRNA) impairs the transmigration of neutrophils and reduces ICAM-1–stimulated phosphorylation of vascular endothelial-cell cadherin (VE-cadherin). Our results reveal a novel role of endothelial Nogo-B in basic immune functions and provide a key link in the molecular network governing endothelial-cell regulation of diapedesis. |
| Related Links | http://www.bloodjournal.org/content/117/7/2284.full.pdf |
| Ending Page | 2295 |
| Page Count | 12 |
| Starting Page | 2284 |
| DOI | 10.1182/blood-2010-04-281956 |
| Journal | Blood |
| Issue Number | 7 |
| Volume Number | 117 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2011-02-17 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Small Interfering Rna Rtn Bone Marrow A/b Regulates Endothelial Nogo Leukocyte Transmigration Journal: Blood (Vol- 100, Issue- 7) |
| Content Type | Text |
| Resource Type | Article |
