| Slit2 regulates attractive eosinophil and repulsive neutrophil chemotaxis through differential srGAP1 expression during lung inflammation. | |
| | |
MedLine Citation:
|
PMID: 20944010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Directional migration of leukocytes is an essential step in leukocyte trafficking during inflammatory responses. However, the molecular mechanisms governing directional chemotaxis of leukocytes remain poorly understood. The Slit family of guidance cues has been implicated for inhibition of leuocyte migration. We report that Clara cells in the bronchial epithelium secreted Slit2, whereas eosinophils and neutrophils expressed its cell-surface receptor, Robo1. Compared to neutrophils, eosinophils exhibited a significantly lower level of Slit-Robo GTPase-activating protein 1 (srGAP1), leading to activation of Cdc42, recruitment of PI3K to Robo1, enhancment of eotaxin-induced eosinophil chemotaxis, and exaggeration of allergic airway inflammation. Notably, OVA sensitization elicited a Slit2 gradient at so-called bronchus-alveoli axis, with a higher level of Slit2 in the bronchial epithelium and a lower level in the alveolar tissue. Aerosol administration of rSlit2 accelerated eosinophil infiltration, whereas i.v. administered Slit2 reduced eosinophil deposition. In contrast, Slit2 inactivated Cdc42 and suppressed stromal cell-derived factor-1α-induced chemotaxis of neutrophils for inhibiting endotoxin-induced lung inflammation, which were reversed by blockade of srGAP1 binding to Robo1. These results indicate that the newly identified Slit2 gradient at the bronchus-alveoli axis induces attractive PI3K signaling in eosinophils and repulsive srGAP1 signaling in neutrophils through differential srGAP1 expression during lung inflammation. |
| | |
Authors:
|
Bu-Qing Ye; Zhen H Geng; Li Ma; Jian-Guo Geng |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-13 |
Journal Detail:
|
Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
|
Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-10-24 |
Medline Journal Info:
|
Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
|
Languages: eng Pagination: 6294-305 Citation Subset: AIM; IM |
Affiliation:
|
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Bronchi / immunology, metabolism Chemotaxis, Leukocyte / physiology* Eosinophils / immunology, metabolism* Fluorescent Antibody Technique GTPase-Activating Proteins / biosynthesis*, immunology Humans Immunoblotting Immunoprecipitation Intercellular Signaling Peptides and Proteins / immunology, secretion* Mice Mice, Inbred C57BL Nerve Tissue Proteins / biosynthesis, immunology, secretion* Neutrophils / immunology, metabolism* Pneumonia / immunology, metabolism* Pulmonary Alveoli / immunology, metabolism Receptors, Immunologic / biosynthesis, immunology Respiratory Hypersensitivity / immunology, metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology |
| Grant Support | |
ID/Acronym/Agency:
|
R01 CA126897-04/CA/NCI NIH HHS; R01AI064743/AI/NIAID NIH HHS; R01CA126897/CA/NCI NIH HHS; R56 AI064743-01A1/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/GTPase-Activating Proteins; 0/Intercellular Signaling Peptides and Proteins; 0/Nerve Tissue Proteins; 0/Receptors, Immunologic; 0/Slit homolog 2 protein; 0/roundabout protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Notch ligand delta-like 4 regulates development and pathogenesis of allergic airway responses by mod...
Next Document: Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental...