| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Sohlbach, Charlotte Abram, Clare Zarbock, Alexander Block, Helena Stadtmann, Anika Lowell, Clifford A. Boras, Mark Volmering, Stephanie |
| Description |
Author Affiliation: Stadtmann A ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany); Block H ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany); Volmering S ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany); Abram C ( Department of Laboratory Medicine, University of California, San Francisco, CA 94143.); Sohlbach C ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany); Boras M ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany); Lowell CA ( Department of Laboratory Medicine, University of California, San Francisco, CA 94143.); Zarbock A ( Department of Anesthesiology, Intensive Care, and Pain Medicine, University of Münster, 48149 Münster, Germany) |
| Abstract |
Neutrophil recruitment to the site of inflammation plays a pivotal role in host defense. However, overwhelming activation and accumulation of neutrophils in the tissue may cause tissue damage and autoimmunity due to the release of cytokines, oxidants, and proteases. Neutrophil adhesion in acute inflammation is initiated by activation of Lß2 (LFA-1), which can be induced by rolling on E-selectin (slowly) or by exposure to the chemokine CXCL1 (rapidly). Despite the clinical importance, cell-intrinsic molecular mechanisms of negative regulation of integrin adhesiveness and neutrophil recruitment are poorly understood. Mice deficient in the tyrosine phosphatase Src homology 2 domain-containing protein tyrosine phosphatase 1 (Shp1) show increased leukocyte adhesion, but the interpretation of these data is limited by the severe global phenotype of these mice. In this study, we used mice with global and myeloid-restricted deletion of Shp1 to study neutrophil arrest, adhesion, crawling, and transendothelial migration in vitro and in vivo. Shp1 deficiency results in increased neutrophil adhesion in vivo; however, neutrophil crawling, transmigration, and chemotaxis were reduced in these mice. Mechanistically, Shp1 binds and controls PIPKIγ activity and, thereby, modulates phosphatidylinositol (4,5)-bisphosphate levels and adhesion. Thus, Shp1 is involved in the deactivation of integrins and regulation of neutrophil recruitment into inflamed tissue. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1500606 |
| Journal |
The Journal of Immunology |
| Issue Number |
3 |
| Volume Number |
195 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-08-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cell Adhesion Immunology Neutrophil Infiltration Phosphatidylinositols Metabolism Phosphotransferases (alcohol Group Acceptor) Protein Tyrosine Phosphatase, Non-receptor Type 6 Animals Genetics Cell Line, Tumor Cell Movement Chemokine Cxcl1 E-selectin Enzyme Activation Hl-60 Cells Inflammation Leukocyte Rolling Lymphocyte Function-associated Antigen-1 Mice Mice, Inbred C57bl Mice, Knockout Neutrophils Biosynthesis Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
