STEM-CELL FACTOR MODULATES AVIDITY OF ALPHA(4)BETA(1) AND ALPHA(5)BETA(1) INTEGRINS EXPRESSED ON HEMATOPOIETIC-CELL LINES

Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of extracellular matrix and stromal cells, are crucial for he matopoiesis. Integrins facilitate these interactions by mediating adhe rence of hematopoietic cells to both the extracellular matrix and stro mal cells. Marrow stromal cells secrete a variety of growth factors, i ncluding stem cell factor (SCF). Because treatment with SCF in vivo mo bilizes primitive hematopoietic cells from the BM, we investigated the effect of the growth factor SCF of hematopoietic cell adhesion. These studies show that SCF modulates adhesive function in a dose- and time -dependent manner, but does not modulate expression of the integrins a lpha(4) beta(1) and alpha(5) beta(1) in the SCF-responsive cell line M O7E. Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine-activated human umbilical vein endo thelial cells (HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1 )-transfected Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This increase i n adhesion was paralleled by increased binding of the beta(1), activat ion-dependent monoclonal antibody (MoAb) 15/7, as determined by flow c ytometry. However, prolonged incubation of MO7E with SCF induced a mar ked decrease in integrin-mediated adherence, with maximal inhibition b y 24 hours. No change in expression of integrins, as determined by flo w cytometry, was observed with short- or long-term incubation with SCF . SCF-treated cells were still able to respond to phorbol esters and t o the activating beta(1), MoAb 8A2 with increased adherence, but not t o the level seen in control cells. This suggests that a subpopulation of expressed alpha(4) beta(1) and alpha(5) beta(1) integrins is diseng aged by prolonged incubation with SCF. (C) 1995 by The American Societ y of Hematology.