G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow

• Published in: Annals of hematology 2014-07, Vol.93 (7), p.1111-1122
• Main Authors: Shimizu, Naomi, Nakaseko, Chiaki, Jiang, Meizi, Nishii, Keigo, Yokote, Koutaro, Iseki, Tohru, Higashi, Morihiro, Tamaru, Junichi, Schneider, Wolfgang Johann, Bujo, Hideaki
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - blood; Bone Marrow - drug effects; Bone Marrow - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematology; Hematopoietic Stem Cell Mobilization - methods; HL-60 Cells; Human Umbilical Vein Endothelial Cells; Humans; Injections, Subcutaneous; LDL-Receptor Related Proteins - blood; LDL-Receptor Related Proteins - secretion; Medicine; Medicine & Public Health; Membrane Transport Proteins - blood; Membrane Transport Proteins - secretion; Mice; Mice, Inbred C57BL; Myeloid Cells - drug effects; Myeloid Cells - physiology; Oncology; Original Article; U937 Cells
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-014-2033-0

Granulocyte colony-stimulating factor (G-CSF) induces the mobilization of leukocytes from the bone marrow (BM) to the circulation by a yet incompletely understood mechanism. Here, we describe that the membrane-bound receptor LR11 is highly expressed in human myeloid cells and that the shed soluble form of LR11 (sLR11) is a modifier of myeloid cell migration. In the process of leukocyte mobilization by G-CSF treatment, circulating sLR11 levels are transiently elevated in humans and mice. Moreover, following G-CSF treatment, the sLR11 levels in patients show significant positive correlation with the numbers of mobilized leukocytes. The changes of LR11 levels in BM cells and of sLR11 released into the BM fluid of mice correlate tightly with the changes in circulating sLR11 levels. G-CSF dose-dependently enhanced sLR11 release from HL-60 cells, which in turn accelerated cell migration. Finally, cooperatively with tumor necrosis factor-α (TNF-α) and G-CSF, sLR11 increased the attachment of floating cells (HL-60 and U937) to endothelial cells. We propose that sLR11 is a novel candidate modifier of G-CSF-mediated mobilization of hematologic cells. Identification of sLR11 as a regulatory component of G-CSF-mediated hematologic cell mobilization may facilitate further improvement of hematologic stem cell collection for clinical applications.