Document Detail


Cell surface localization and release of the candidate tumor suppressor Ecrg4 from polymorphonuclear cells and monocytes activate macrophages.
MedLine Citation:
PMID:  22396620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We identified fresh human leukocytes as an abundant source of the candidate epithelial tumor suppressor gene, Ecrg4, an epigenetically regulated gene, which unlike other tumor suppressor genes, encodes an orphan-secreted, ligand-like protein. In human cell lines, Ecrg4 gene expression was low, Ecrg4 protein undetectable, and Ecrg4 promoter hypermethylation high (45-90%) and reversible by the methylation inhibitor 5-AzaC. In contrast, Ecrg4 gene expression in fresh, normal human PBMCs and PMNs was 600-800 times higher than in cultured cell lines, methylation of the Ecrg4 promoter was low (<3%), and protein levels were readily detectable in lysates and on the cell surface. Flow cytometry, immunofluorescent staining, and cell surface biotinylation established that full-length, 14-kDa Ecrg4 was localized on PMN and monocyte cell surfaces, establishing that Ecrg4 is a membrane-anchored protein. LPS treatment induced processing and release of Ecrg4, as detected by flow and immunoblotting, whereas an effect of fMLF treatment on Ecrg4 on the PMN cell surface was detected on the polarized R2 subpopulation of cells. This loss of cell surface Ecrg4 was associated with the detection of intact and processed Ecrg4 in the conditioned media of fresh leukocytes and was shown to be associated with the inflammatory response that follows severe, cutaneous burn injury. Furthermore, incubation of macrophages with a soluble Ecrg4-derived peptide increased the P-p65, suggesting that processing of an intact sentinel Ecrg4 on quiescent circulating leukocytes leads to processing from the cell surface following injury and macrophage activation.
Authors:
Andrew Baird; Raul Coimbra; Xitong Dang; Nicole Lopez; Jisook Lee; Michael Krzyzaniak; Robert Winfield; Bruce Potenza; Brian P Eliceiri
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, American Recovery and Reinvestment Act; Research Support, N.I.H., Extramural     Date:  2012-03-06
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  91     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-01     Completed Date:  2012-06-21     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  773-81     Citation Subset:  IM    
Affiliation:
University of California San Diego School of Medicine, 212 Dickinson St., MC 8236, San Diego, CA 92103, USA. anbaird@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
BALB 3T3 Cells
Blotting, Western
Burns / metabolism*
Case-Control Studies
Cells, Cultured
DNA Methylation
Flow Cytometry
Genes, Tumor Suppressor*
Humans
Leukocytes / cytology,  metabolism*
Macrophage Activation
Macrophages, Peritoneal / metabolism*
Mice
Monocytes / metabolism*
Neoplasm Proteins / genetics,  metabolism*
Neutrophils / cytology,  metabolism
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
DK085871/DK/NIDDK NIH HHS; EY018479/EY/NEI NIH HHS; HL73396/HL/NHLBI NIH HHS; P20 GM078421/GM/NIGMS NIH HHS; P20-GM078421/GM/NIGMS NIH HHS; T32 CA106493/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/C2orf40 protein, human; 0/Neoplasm Proteins; 0/RNA, Messenger
Comments/Corrections

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