Title | Endothelial reticulon-4B (Nogo-B) regulates ICAM-1-mediated leukocyte transmigration and acute inflammation. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Di Lorenzo A, Manes TD, Davalos A, Wright PL, Sessa WC |
Journal | Blood |
Volume | 117 |
Issue | 7 |
Pagination | 2284-95 |
Date Published | 2011 Feb 17 |
ISSN | 1528-0020 |
Keywords | Animals, Antigens, CD, Cadherins, Carrageenan, Cell Movement, Endothelial Cells, Focal Adhesion Kinase 2, Humans, In Vitro Techniques, Inflammation, Intercellular Adhesion Molecule-1, Leukocytes, Macrophages, Male, Mice, Mice, Congenic, Mice, Knockout, Monocytes, Myelin Proteins, Neutrophils, Nogo Proteins, Phosphorylation, RNA, Small Interfering, Signal Transduction, src-Family Kinases |
Abstract | 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. |
DOI | 10.1182/blood-2010-04-281956 |
Alternate Journal | Blood |
PubMed ID | 21183689 |
PubMed Central ID | PMC3062334 |
Grant List | R01 HL61371 / HL / NHLBI NIH HHS / United States R01 HL64793 / HL / NHLBI NIH HHS / United States P01 HL70295 / HL / NHLBI NIH HHS / United States |
Related Lab:
Related Faculty:
Annarita Di Lorenzo, Ph.D.