| Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation. | |
| | |
MedLine Citation:
|
PMID: 20691665 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Apoptotic cell removal (efferocytosis) is an essential process in the regulation of inflammation and tissue repair. We have shown that monocyte chemoattractant protein-1/CC chemokine ligand 2 (MCP-1/CCL2) enhances efferocytosis by alveolar macrophages in murine bacterial pneumonia. However, the mechanism by which MCP-1 exerts this effect remains to be determined. Here we explored that hypothesis that MCP-1 enhances efferocytosis through a Rac1/phosphatidylinositol 3-kinase (PI3-kinase)-dependent mechanism. We assessed phagocytosis of apoptotic cells by MCP-1 treated murine macrophages in vitro and in vivo. Rac activity in macrophages was measured using a Rac pull down assay and an ELISA based assay (GLISA). The downstream Rac1 activation pathway was studied using a specific Rac1 inhibitor and PI3-kinase inhibitor in in vitro assays. MCP-1 enhanced efferocytosis of apoptotic cells by murine alveolar macrophages (AMs), peritoneal macrophages (PMs), the J774 macrophage cell line (J774s) in vitro, and murine AMs in vivo. Rac1 activation was demonstrated in these cell lines. The effect of MCP-1 on efferocytosis was completely negated by the Rac1 inhibitor and PI3-kinase inhibitor. We demonstrated that MCP-1 enhances efferocytosis in a Rac1-PI3 kinase-dependent manner. Therefore, MCP-1-Rac1-PI3K interaction plays a critical role in resolution of acute lung inflammation. |
| | |
Authors:
|
Takeshi Tanaka; Mayumi Terada; Koya Ariyoshi; Konosuke Morimoto |
Related Documents
:
|
9653095 - In vivo inhibition of cc and cx3c chemokine-induced leukocyte infiltration and attenuat... 10857785 - Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced ar... 7503075 - Chemokines and renal disease. 17557195 - Cell motility and cytoskeletal regulation in invasion and metastasis. 309295 - Inhibitory activity of unstimulated alveolar macrophages on t-lymphocyte blastogenic re... 3534085 - Immunomodulating effect of autohaemotherapy (a literature review). |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-05 |
Journal Detail:
|
Title: Biochemical and biophysical research communications Volume: 399 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-09-06 Completed Date: 2010-10-07 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
|
Languages: eng Pagination: 677-82 Citation Subset: IM |
Copyright Information:
|
Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
1-Phosphatidylinositol 3-Kinase
/
metabolism Animals Apoptosis* Chemokine CCL2 / metabolism*, pharmacology Enzyme Activation Macrophages, Alveolar / drug effects, enzymology, immunology* Mice Mice, Inbred BALB C Mice, Inbred ICR Neuropeptides / biosynthesis* Phagocytosis Pneumonia / immunology* Receptors, CCR2 / metabolism Recombinant Proteins / pharmacology Up-Regulation rac GTP-Binding Proteins / biosynthesis* |
| Chemical | |
Reg. No./Substance:
|
0/Ccl2 protein, mouse; 0/Ccr2 protein, mouse; 0/Chemokine CCL2; 0/Neuropeptides; 0/Rac1 protein, mouse; 0/Receptors, CCR2; 0/Recombinant Proteins; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 3.6.5.2/rac GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Foxn3 is essential for craniofacial development in mice and a putative candidate involved in human c...
Next Document: The NH(2)-terminus of K(+)-Cl(-) cotransporter 3a is essential for up-regulation of Na(+),K(+)-ATPas...