G-CSF increases the expression of VCAM-1 on stromal cells promoting the adhesion of CD34+ hematopoietic cells: studies under flow conditions.
OBJECTIVE
The knowledge of the mechanisms underlying the adhesive processes that lead to homing and/or mobilization of hematopoietic progenitor cells, and the influence of blood rheology, is still limited. We analyzed the impact of flow conditions on the adhesion of CD34+ peripheral blood progenitor cell (PBPC) to the adhesive proteins fibronectin, laminin, and collagen, and to stromal cells.


RESULTS
Under static conditions, all the adhesive substrata assayed promoted adhesion of CD34+ PBPC, being higher on the stromal cells. Under flow conditions, adhesion of CD34+ PBPC was remarkable on stromal cells while insignificant onto the purified proteins. Exposure of stromal cell monolayers to granulocyte colony-stimulating factor (G-CSF) further enhanced PBPC adhesion. This effect correlated with the activation of p38 MAPK and with an increase in the expression of VCAM-1 on stromal cells exposed to G-CSF. In inhibitory assays, both an antibody to the G-CSFR and a specific inhibitor of the p38 MAPK blocked the effects induced by the cytokine.


CONCLUSIONS
Our results provide direct evidence that in stromal cells G-CSF activates the signaling protein p38 MAPK, inducing expression of the adhesion receptor VCAM-1. This mechanism seems to promote adhesion of CD34+ cells on stromal cells and could play a potential role in homing events.
Fuste
Berta
B
Servicio de Hemoterapia-Hemostasia, Hospital Clínic, IDIBAPS, Barcelona, Spain.
Escolar
Gines
G
Marin
Pedro
P
Mazzara
Roberto
R
Ordinas
Antonio
A
Diaz-Ricart
Maribel
M
D018952:Antigens, CD34 / Q000032:analysis*; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D017154:Stromal Cells / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D018952:Antigens, CD34; D019010:Vascular Cell Adhesion Molecule-1; D016179:Granulocyte Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases