DEK, a nuclear protein, is chemotactic for hematopoietic stem/progenitor cells acting through CXCR2 and Gαi signaling

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Maegan L. Capitano¹  Yasser Sammour¹  James Ropa¹  Maureen Legendre²  Nirit Mor-Vaknin²  David M. Markovitz² 

[1] Department of Microbiology and Immunology, Indiana University School of Medicine;Department of Internal Medicine, Division of Infectious Diseases, University of Michigan

关键词: chemokines;    chemotaxis;    CXCR2;    DEK;    Gαi signaling;    hematopoietic stem and progenitor cells;   

DOI  :  10.1002/JLB.3AB1120-740R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell-derived factor 1α (SDF1α/CXCL12) being the most potent known such protein. DEK, a nuclear DNA-binding chromatin protein with hematopoietic cytokine-like activity, is a chemotactic factor attracting mature immune cells. Transwell migration assays were performed to test whether DEK serves as a chemotactic agent for HSC/HPC. DEK induced dose- and time-dependent directed migration of lineage negative (Lin – ) Sca-1 + c-Kit + (LSK) bone marrow (BM) cells, HSCs and HPCs. Checkerboard assays demonstrated that DEK's activity was chemotactic (directed), not chemokinetic (random migration), in nature. DEK and SDF1α compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting Gαi protein signaling with Pertussis toxin pretreatment inhibited migration of LSK cells toward DEK. Thus, DEK is a novel and rare chemotactic agent for HSC/HPC acting in a direct or indirect CXCR2 and Gαi protein-coupled signaling-dependent manner.

【 授权许可】

CC BY