SDF-1-induced actin polymerization and migration in human hematopoietic progenitor cells.
OBJECTIVE
The capacity of hematopoietic progenitor cells (HPCs; CD34(+) cells) to respond to chemotactic stimulation is essential for their homing efficiency, e.g., during stem cell transplantation. Previous studies established that stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 play an important role in the homing of HPCs. The aim of the present study was to analyze SDF-1-induced actin polymerization and migration of HL-60 cells and primary human CD34(+) cells.


METHODS
SDF-1-induced migration of CD34(+) cells from cord blood (CB) and peripheral blood (PB) across fibronectin-coated filters was measured in a Transwell assay. Actin polymerization was detected using fluorescent phalloidin and analyzed by confocal microscopy and FACS analysis.


RESULTS
SDF-1 induced a rapid and transient increase in actin polymerization and in polarization of the actin cytoskeleton in primary CD34(+) cells and HL-60 cells. SDF-1 was found to induce significantly more actin polymerization in CB CD34(+) cells that show fast migration in vitro compared to slow migrating PB CD34(+) cells. Moreover, CB CD34(+) cells that had migrated toward SDF-1 showed an elevated and prolonged rise in F-actin upon second exposure to SDF-1 compared to nonmigrated cells, although both cell types expressed equal levels of the SDF-1 receptor CXCR-4.


CONCLUSIONS
The relatively high migratory capacity of CB-derived human HPCs is not related to cellular polarization or high expression of the SDF-1 receptor but is largely determined by their capacity to efficiently polymerize F-actin in response to SDF-1.
Voermans
C
C
Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Anthony
E C
EC
Mul
E
E
van der Schoot
E
E
Hordijk
P
P
D000199:Actins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D005260:Female; D018922:HL-60 Cells; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008223:Lymphoma / Q000473:pathology*; D013997:Time Factors
D000199:Actins; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC