Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic progenitor cells.
Stromal cell-derived factor-1alpha (SDF-1alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1. It is required during hematopoiesis and homing of HPC to the BM. As HPC migration in response to SDF-1alpha might require dynamic regulation of integrin function, we investigated if SDF-1alpha could modulate VLA-4 function on BM CD34(hi) cells.CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1alpha on VLA-4-dependent adhesion to CS-1/fibronectin and VCAM-1, as well as to BM stroma. CD34(hi) BM cells that adhered to VLA-4 ligands after SDF-1alpha treatment were characterized in colony-forming and long-term culture-initiating cell (LTC-IC) assays.SDF-1alpha rapidly (1 minute) and transiently upregulated the adhesion of CD34(hi) BM cells and hematopoietic cell lines to both CS-1/fibronectin and VCAM-1, and to BM stromal cells. The upregulation of VLA-4-dependent cell adhesion by SDF-1alpha targeted primitive LTC-IC as well as committed CD34(hi) cells. SDF-1alpha-triggered enhancement in VLA-4 function was inhibited by pertussis toxin (PTx) and cytochalasin D, indicating the involvement of G(i) protein downstream signaling and an intact cytoskeleton. Instead, activation of p44/42 MAP kinases by SDF-1alpha did not functionally correlate with enhancement of VLA-4-dependent cell adhesion. Modulation of VLA-4-mediated CD34(hi) BM cell adhesion by SDF-1alpha could play a key role in their migration within and to the BM and therefore influence their proliferation and differentiation.
Centro de Investigaciones Biológicas, Department of Immunology, Madrid, Spain.
A
A
Hidalgo
F
F
Sanz-Rodríguez
J L
JL
Rodríguez-Fernández
B
B
Albella
C
C
Blaya
N
N
Wright
C
C
Cabañas
F
F
Prósper
J C
JC
Gutierrez-Ramos
J
J
Teixidó
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005353:Fibronectins / Q000378:metabolism*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007947:Leukemia, Megakaryoblastic, Acute / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology; D019718:Receptors, CXCR4 / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C424122:FN-H89 fibronectin fragment; D005353:Fibronectins; D016298:Hematopoietic Cell Growth Factors; D039041:Integrin alpha4beta1; D016023:Integrins; D010446:Peptide Fragments; D019718:Receptors, CXCR4; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1