STIMULATION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) PRODUCTION AND ITS ROLE AS AN AUTOCRINE INDUCER OF CD14 UP-REGULATION IN HUMAN MYELOID-LEUKEMIA CELLS

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotr opic cytokine that takes part in the growth and differentiation of nor mal and leukemic hematopoietic cells, Because of its potential signifi cance in the etiopathogenesis of myeloid leukemia, we have studied the extracellular stimuli leading to GM-CSF secretion from a human myeloi d leukemia cell line, K-562, and have demonstrated an important role f or the cytokine in the differentiation process of this cell line, TNF- alpha, IL-1 beta, phorbol ester (PMA), and calcium ionophore A23187 we re found to stimulate GM-CSF production from K-562 cells, PMA caused t he cells to differentiate into megakaryocytic lineage, whereas treatme nt with A23187 resulted in increased expression of monocyte/macrophage marker CD14, Neutralization of the GM-CSF activity in the culture med ium, as well as blocking of its receptors, resulted in suppression of the increase in CD14 expression and partially restored the proliferati ve capacity in cells exposed to A23187, Autocrine GM-CSF secretion did not appear to play an important role in PMA-induced megakaryocytic di fferentiation. These results suggest that autocrine GM-CSF secretion m ay be associated with differentiation of myeloid leukemic cells withou t any significant growth stimulatory activity.