Differentiation of human promyelocytic leukemia cell line HL60 by microbial extracellular glycolipids

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Abstract
Microbial extracellular glycolipids, succinoyl trehalose lipid (STL), and mannosylerythritol lipid (MEL) inhibited the growth of a human promyelocytic leukemia cell line, HL60, and induced their morphological changes. The results of specific and nonspecific leukocyte esterase activities showed that STL induced monocytotic differentiation while MEL induced granulocytic differentiation. STL and MEL markedly increased common differentiation-associated characteristics in monocytes and granulocytes, such as nitroblue tetrazolium (NBT) reducing ability, expression of Fc receptors, and phagocytic activities in HL60 cells, respectively. Neither sugar moieties nor fatty acids in the free form, the individual components of STL and MEL, were effective at inducing the differentiation of HL60 cells. The induction of differentiation was not due to surface activities of STL and MEL on the basis of the complete ineffectiveness of the analogues tested. The composition of cell surface glycosphingolipids (GSL) changed such that the GM3/LacCer ratio increased in STL-treated cells, whereas it decreased in MEL-treated cells. HL60 cells treated with STL and MEL exhibited a significant decrease in the activity of the intracellular phospholipid- and Ca2+-dependent protein kinase (protein kinase C). Furthermore, the serine/threonine phosphorylations in intact HL60 cells were clearly inhibited by the presence of GM3 and MEL, but not by LacCer and STL. These results suggest that the differentiation-inducing activity of STL and MEL is not due to a simple detergent-like effect but due to a specific action on the plasma membrane. The inhibitory effect of STL on protein kinase activity was through increasing GM3, but MEL had a direct inhibitory effect.

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