Macrophage inflammatory protein 1α enhances in a different manner adhesion of hematopoietic progenitor cells from bone marrow, cord blood, and mobilized peripheral blood

Abstract

Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor, and thrombopoietin were reported to upregulate the adhesion of hematopoietic progenitors to immobilized fibronectin through activation of integrin α4β1 and α5β1. Macrophage inflammatory protein (MIP)-1α is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro. We asked if MIP-1α would modulate the adhesive phenotype of colony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cord blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparison with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1α significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1α were inhibited by blocking antibodies to integrin α4, α5, or β1, and polymerization plus rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of MIP-1α on the adhesive phenotype of CFCs is mediated by modulation of the organization of integrin. The amount of MIP-1α receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in the adhesive response induced by MIP-1α. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect to maturation, integrin affinity, MIP-1α receptor expression, and regulation of MIP-1α signaling. Our data indicate that MIP-1α may affect migration, homing, and mobilization of hematopoietic progenitors by modulating the adhesive phenotype of these cells.