[rhTGF-beta 1 induced differentiation of human promonocytic leukemia THP-1 cells].
With promonocytic leukemia cell line THP-1 cells as an experimental material, the present paper described the proliferation, differentiation and maturation of these cells into m phi-like cells when they were treated with rhTGF-beta 1. Both cell number count and 3H-TdR uptake experiments indicated that rhTGF-beta 1 obviously inhibited the proliferation of THP-1 cells, and the inhibiting effect was related to its concentration. At the same time, the changes in the mode of cell growth and morphology occurred. The cells changed gradually from suspensive into adherent state and formed two groups of cell populations. The number of adherent cells formed was dependent on the concentration and duration of the treatment of rhTGF-beta 1. Therefore, based on the degree of inhibition of cell proliferation and the number of adherent cells with different rhTGF-beta 1 concentrations in a trial experiment, 1.25 ng/ml rhTGF-beta 1 was chosen as the dose in other experiments. From scanning electronmicroscopic observation, it was found that the external morphology of rhTGF-beta 1 treated THP-1 cells gradually transformed into typical macrophage-like cells. Concomitantly, their subcellular organelles also became progressively matured, with primary lysosomes typical for early M phi in 72 h and secondary lysosomes and phagosomes for mature M phi in 120 h of induction, as observed with transmission electron microscope. The ANAE activity, NBT reduction and phagocytosis of differentiated adherent cells were higher than those of control cells and suspensive cells. Specific anti-human TGF-beta-neutralizing mAb could completely block the differentiation of THP-1 cells into M phi-like cells. To sum up, from the results of the studies on cell morphology, growth mode, ultrastructures, phagocytosis, enzyme activation and TGF-beta 1 mAb blocking of induction and differentiation, it is clear that rhTGF-beta 1 can induce THP-1 cells to differentiate and mature into M phi-like cells, with the parallel development of cytoplasmic organoids, phenotype variation and the gaining of phagocytosis activity etc. Concordantly, rhTGF-beta 1 made the M phi-like cells to an activated state as they became matured during the induced differentiation.
Yu
G H
GH
Shanghai Institute of Cell Biology, Chinese Academy of Sciences.
Ge
X R
XR
Yao
Z
Z
D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta