title: G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow.
abstract: 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.
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
authors.forename: Meizi
authors.initials: M
authors.lastname: Jiang
authors.forename: Keigo
authors.initials: K
authors.lastname: Nishii
authors.forename: Koutaro
authors.initials: K
authors.lastname: Yokote
authors.forename: Tohru
authors.initials: T
authors.lastname: Iseki
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higashi
authors.forename: Junichi
authors.initials: J
authors.lastname: Tamaru
authors.forename: Wolfgang Johann
authors.initials: WJ
authors.lastname: Schneider
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bujo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D018922:HL-60 Cells; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007279:Injections, Subcutaneous; D026502:LDL-Receptor Related Proteins / Q000097:blood* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000097:blood* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000187:drug effects / Q000502:physiology*; D020298:U937 Cells
chemical_list: D015415:Biomarkers; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human; D016179:Granulocyte Colony-Stimulating Factor