5,8,11,14-eicosatetraynoic acid-induced differentiation of U937 cells

U937 cells, transformed human monocyte/macrophage precursors, incubated with 5,8,11,14 eicosatetraynoic acid (ETYA), a competitive in vitro and in vivo inhibitor of arachidonic acid, develop properties consistent with a form of cellular differentiation. In order to define the extent of this differentiation and decide whether a monocyte or macrophage-like cell developed, control cells and cells cultured for three days with 40 microns ETYA were examined by transmission electron microscopy. Control cells were characterized by oval nuclei, a high nuclear to cytoplasmic ratio, a cytoplasm with a relative paucity of mitochondria, vesicles and vacuoles, and a Golgi apparatus that was not extensively developed. Ribosomes and putative ribosome-like granules were frequently "grouped" in the cytoplasm, rather than as single granules or in association with the endoplasmic reticulum. The plasma membrane included a discrete region of fimbriated structures that were distinct from pseudopodia. Such structures frequently are expressed in embryonic and transformed cells and may be associated with motility, metastases, with immunologic reactions or with endocytosis. After culture with 40 microns ETYA for three or more days, a morphology consistent with that of immature monocytes developed. These characteristics included lobulated nuclei, a reversal of the nuclear to cytoplasmic ratio, an increased complexity and development of the cytoplasmic components and the disappearance of the fimbriated plasma membrane structures. In addition, "grouped" ribosomes were less evident.(ABSTRACT TRUNCATED AT 250 WORDS)