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The Role of Fatty Acid Metabolites in the Differentiation of the Human Monocyte‐Like Cell Line U937
Author(s) -
Bomalaski John S.,
Freundlich Bruce,
Steiner Sheldon,
Clark Mike A.
Publication year - 1988
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.44.1.51
Subject(s) - biology , monocyte , u937 cell , cell culture , fatty acid , microbiology and biotechnology , cellular differentiation , line (geometry) , biochemistry , immunology , genetics , gene , geometry , mathematics
Abstract The human monocyte cell line, U937, can be induced to terminally differentiate into macrophage‐like cells when treated with gamma‐interferon. However, if these cells were treated with gamma‐interferon and esculetin, an inhibitor of the lipoxygenase pathway, or BW755C, an inhibitor of both the lipoxygenase and the cyclooxygenase pathways, a marked inhibition in cellular differentiation occurred. In contrast, inhibitors of only the cyclooxygenase pathway had no effect on differentiation. These studies suggest a role for lipoxygenase products of arachidonic acid in the differentiation of the human U937 cell line. Arachidonic acid utilized in the production of eicosanoids is derived from phospholipids by the action of phospholipase A 2 and phospholipase C. When U937 cells were cultured in medium supplemented with gamma‐interferon, there was a striking increase in the level of phosphatidylcholine and phosphatidylethanolamine‐specific phospholipase A 2 activities and phosphatidylinositol‐specific phospholipase C activity as compared to control cells. Morever, although there was not a significant difference in the incorporation of labeled arachidonic acid or linoleic acid into the major phospholipids of differentiated U937 cells as compared to undifferentiated control cells, there was a marked increase in the relative amount of the labeled arachidonic acid released from the differentiated cells as lipoxygenase products compared to cyclooxygenase products. These data suggest that lipoxygenase products may be essential in the differentiation process of U937 cells and that enhanced phospholipase enzyme activities that occur during differentiation help explain how arachidonic acid becomes available to form lipoxygenase products.