GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR DOES NOT SUPPORT ROLLING OF PROMYELOCYTIC LEUKEMIC CELLS UNDER FLOW

摘要

Leukocytes and HL-60 leukemic cells both express P-selectin glycoprotein ligand-1 (PSGL-1), a high-affinity ligand to P-selectin. During inflammatory response, P-selectin is upregulated on post-capillary venules and mediates rolling of leukocytes. This response is critical for host survival. HL-60 leukemic cells also roll on P-selectin surfaces and but for the ubiquity of P-selectin/PSGL-1 interactions of normal leukocytes, targeted liposomal delivery systems using selectins would be a potential new approach to anticancer therapy. Other HL-60 membrane proteins are less commonly expressed and hence are potential targeting molecules for use in liposomal delivery systems. We tested the granulocyte macrophage colony-stimulating factor receptor (GM-CSFr) for its ability to mediate rolling interactions. HL-60 cells were perfused over GM-CSF or P-selectin surfaces overa range of physiologically relevant wall shear stresses. The cell rolling velocity over P-selectin surfaces was reasonably stable, incurring a 4-6 fold increase in velocity (depending on incubation concentration) while being subjected to an approximate 10-fold increase in shear stress. HL-60 cells did not interact with GM-CSF functionalized surface under any of the incubation concentrations tested leading us to reject the hypothesis that GM-CSF would mediate rolling interactions.