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  • Title: G-CSF increases the expression of VCAM-1 on stromal cells promoting the adhesion of CD34+ hematopoietic cells: studies under flow conditions.
    Author: Fuste B, Escolar G, Marin P, Mazzara R, Ordinas A, Diaz-Ricart M.
    Journal: Exp Hematol; 2004 Aug; 32(8):765-72. PubMed ID: 15308328.
    Abstract:
    OBJECTIVE AND METHODS: 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. CONCLUSION: 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.
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