DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINE HL60 BY MICROBIAL EXTRACELLULAR GLYCOLIPIDS

Microbial extracellular glycolipids, succinoyl trehalose lipid (STL), and mannosylerythritol lipid (MEL) inhibited the growth of a human pro myelocytic leukemia cell line, HL60, and induced their morphological c hanges. The results of specific and nonspecific leukocyte esterase act ivities showed that STL induced monocytotic differentiation while MEL induced granulocytic differentiation. STL and MEL markedly increased c ommon differentiation-associated characteristics in monocytes and gran ulocytes, such as nitroblue tetrazolium (NBT) reducing ability, expres sion of Fc receptors, and phagocytic activities in HL60 cells, respect ively. Neither sugar moieties nor fatty acids in the free form, the in dividual components of STL and MEL, were effective at inducing the dif ferentiation of HL60 cells. The induction of differentiation was not d ue to surface activities of STL and MEL on the basis of the complete i neffectiveness of the analogues tested. The composition of cell surfac e glycosphingolipids (GL) changed such that the G(M3)/LacCer ratio inc reased 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 pr esence of G(M3) and MEL, but not by LacCer and STL. These results sugg est that the differentiation-inducing activity of STL and MEL is not d ue to a simple detergent like effect but due to a specific action on t he plasma membrane. The inhibitory effect of STL on protein kinase act ivity was through increasing G(M3), but MEL had a direct inhibitory ef fect.