Please note that eDoc will be permanently shut down in the first quarter of 2021!      Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents



  history
ID: 648320.0, MPI für molekulare Biomedizin / Yearbook 2013
Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury
Authors:Block, H.; Herter, J. M.; Rossaint, J.; Stadtmann, A.; Kliche, S.; Lowell, C. A.; Zarbock, A.
Date of Publication (YYYY-MM-DD):2012-02-13
Title of Journal:J Exp Med
Volume:209
Issue / Number:2
Start Page:407
End Page:421
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice. By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kgamma (phosphoinositide 3-kinase-gamma)- and PLCgamma2 (phospholipase Cgamma2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans.
Free Keywords:Adaptor Proteins, Signal Transducing/genetics/immunology/*metabolism; Animals; Cell Line, Tumor; Class Ib Phosphatidylinositol 3-Kinase/metabolism; E-Selectin/metabolism; Genetic Vectors; Humans; Integrins/metabolism; Kidney/*blood supply/*immunology; Leukocyte Rolling/*immunology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neutrophils/*immunology; Peritonitis/chemically induced/immunology; Phospholipase C gamma/metabolism; Phosphoproteins/genetics/immunology/*metabolism; Protein-Tyrosine Kinases/metabolism; Reperfusion Injury/*immunology; Retroviridae; Thioglycolates/toxicity; Transduction, Genetic
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1540-9538 (Electronic) 0022-1007 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/22291096 [ID No:2]
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.