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

Regulatory mechanisms governing adhesion of hematopoietic progenitor cells to the stromal nische are poorly understood. Growth factors such as stem ce ll factor (SCF), granulocyte-macrophage colony-stimulating factor, and thro mbopoietin were reported to upregulate the adhesion of hematopoietic progen itors to immobilized fibronectin through activation of integrin alpha 4 bet a 1 and alpha 5 beta 1. Macrophage inflammatory protein (MIP)-1 alpha. is a C-C chemokine that suppresses colony formation by stem/progenitor cells in vitro, We asked if MIP-1 alpha would modulate the adhesive phenotype of co lony-forming cells (CFCs) obtained from healthy donor bone marrow (BM), cor d blood (CB), and mobilized peripheral blood (mPB) CD34+ cells, in comparis on with SCF, using immobilized fibronectin. SCF significantly increased the level of adhesion of CFCs from BM, CB, and mPB. On the other hand, MIP-1 a lpha significantly increased the level of adhesion of CFCs from BM and CB, but less so from mPB. The effects of MIP-1 alpha were inhibited by blocking antibodies to integrin alpha 4, alpha 5, or beta 1, and polymerization plu s rearrangement of F-actin were observed in affected cells by labeling with rhodamine-conjugated phalloidine. These data indicate that the effect of M IP-1 alpha on the adhesive phenotype of CFCs is mediated by modulation of t he organization of integrin. The amount of MIP-1 alpha receptor on mPB was less than for BM or CB, which may explain the distinct characteristics in t he adhesive response induced by MIP-1 alpha. We suggest that hematopoietic progenitor cells from different sources may be heterogeneous with respect t o maturation, integrin affinity, MIP-1 alpha receptor expression, and regul ation of MIP-1 alpha signaling. Our data indicate that MIP-1 alpha may affe ct migration, homing, and mobilization of hematopoietic progenitors by modu lating the adhesive phenotype of these cells. (C) 1999 International Societ y for Experimental Hematology. Published by Elsevier Science Inc.