The subcellular distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils

Journal of Translational Medicine

Keith M Skubitz³  Raji A Shankar¹  David F Stroncek² 

[1] 3M Corporation, St. Paul, Minnesota, USA;Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA;The Department of Medicine, The University of Minnesota Medical School and Masonic Cancer Center, Minneapolis, Minnesota, USA

关键词: calprotectin;    macrophages;    neutrophils;    MRP14;    myeloid-related protein 14;    MRP8;    Myeloid-related protein 8;   

Others  :  1208480
DOI  :  10.1186/1479-5876-3-36

 received in 2005-07-06, accepted in 2005-09-28,  发布年份 2005

【 摘 要 】

Background

Myeloid-related protein 8 (MRP8) and MRP14 are S100 family calcium binding proteins that form a heterodimer known as calprotectin or MRP8/14 that is present in the cytosol of neutrophils and monocytes. MRP8/14 becomes associated with endothelium at sites of monocyte and neutrophil adhesion and transmigration and induces a thrombogenic and inflammatory response by increasing the endothelial transcription of proinflamatory chemokines and adhesion molecules. The distribution of MRP8/MRP14 among neutrophil granules and plasma membranes is unclear and was investigated to better understand the role of this molecule in acute inflammation.

Study design

Three monoclonal antibodies specific for MRP8 and MRP14 were characterized and used in immunoblotting assays of neutrophil whole cell extracts, and isolated plasma membranes, primary granules, secondary granules and cytosol.

Results

MRP8 and MRP14 were detected in neutrophil cytosol, plasma membrane, primary granule and secondary granule fractions. MRP8/14 demonstrated a calcium-dependent adherence to plasma membranes and primary granules and could be removed by washing with EGTA in a high ionic strength buffer. In contrast, MRP8/14 was found within the contents of the secondary granules. Activated neutrophils released secondary granules and MRP8/14.

Conclusion

MRP8/14 is located in neutrophil cytosol and secondary granule fractions and is loosely associated with plasma membranes. MRP8/14 released with secondary granules by activated neutrophils likely binds to endothelium and plays an important role in acute inflammation.

【 授权许可】

   
2005 Stroncek et al; licensee BioMed Central Ltd.

【 图 表 】

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