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

Few cytokines/growth modulating proteins are known to be chemoattractants for hematopoietic stem (HSC) and progenitor cells (HPC); stromal cell-derived factor 1 alpha (SDF1 alpha/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 SDF1 alpha compete for HSC/HPC chemotaxis. Blocking CXCR2 with neutralizing antibodies or inhibiting G alpha i 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 G alpha i protein-coupled signaling-dependent manner.