Release of platelet-activating factor from HL-60 human leukemic cells following macrophage-like differentiation.
Platelet-activating factors (PAF), a phospholipid mediator of anaphylaxis, is also known to be released in vitro from both phagocytic polymorphonuclear neutrophils (PMN) and monocytes in response to a variety of stimuli. The fact that human myeloid cells of the HL-60 line can be made to differentiate in vitro into macrophage-like cells by 12-O-tetradodecanoylphorbol-13-acetate (TPA) prompted us to investigate the generation and release of PAF during this transformation. Both passive release of PAF at pH 9.5, and active release, following phagocytosis of C3b- and C3d-opsonized yeast spores, and stimulation with C5a anaphylatoxin from untreated and TPA-treated HL-60 cells, PMN, and plastic-adherent normal human monocytes were studied. It was found that after 3 days of TPA treatment, HL-60 cells released PAF following phagocytosis of C3b- and C3d-opsonized yeast spores. Inhibition of PAF release by a selective inhibitor of phospholipase A2 and labeling of PAF with sodium 14C-acetate indicated that PAF generation is a two-step process: (1) release of PAF precursor from cell membranes and (2) its acetylation. A model for the in vivo study of mechanisms and metabolic events involved in PAF generation and release could perhaps be built on these findings.U
D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D010972:Platelet Activating Factor; D011951:Receptors, Complement / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D011951:Receptors, Complement; D013755:Tetradecanoylphorbol Acetate