Yamaguchi M, Hirayoshi K, Okuma M, Nagata K
Department of Cell Biology, Chest Disease Research Institute, Kyoto, Japan.
J Cell Physiol. 1994 Jun;159(3):441-9. doi: 10.1002/jcp.1041590308.
We examined the effect of ATP on the terminal differentiation of mouse myelomonocytic leukemic M1 cells to macrophages. Although ATP alone did not induce M1 cell differentiation, addition of ATP with the differentiation inducer, interleukin 6 (IL-6), enhanced the induction of differentiation by IL-6 about two-fold. Comparison among several adenine nucleotides revealed that the order of effectiveness on differentiation enhancement was ATP > ADP > AMP > or = adenosine. Using reactive blue 2, a P2 receptor antagonist, we confirmed that the effect of ATP on the stimulation of differentiation was mediated through the P2 purinergic receptor. Examination of cytosolic [Ca2+] elevation by ATP and comparison of potency of differentiation enhancement among several ATP analogs demonstrated that the effect of differentiation enhancement was mediated through P2y purinergic receptors expressed on M1 cell surface. Within 3 h of exposure, ATP alone slightly increased the expression of differentiation-related immediate early response genes, c-myc and JunB, and ATP also enhanced the IL-6-induced expression of these genes. Induction of JunB expression by ATP analogs correlated with their potency of differentiation enhancement, which suggested that induction of JunB by ATP is one of signaling pathways involved in the exertion of its differentiation-enhancing effect.
我们研究了三磷酸腺苷（ATP）对小鼠骨髓单核细胞白血病M1细胞向巨噬细胞终末分化的影响。尽管单独的ATP不会诱导M1细胞分化，但将ATP与分化诱导剂白细胞介素6（IL-6）一起添加时，可使IL-6诱导的分化增强约两倍。对几种腺嘌呤核苷酸的比较显示，增强分化效果的有效性顺序为ATP＞二磷酸腺苷（ADP）＞一磷酸腺苷（AMP）≥腺苷。使用P2受体拮抗剂活性蓝2，我们证实ATP对分化刺激的作用是通过P2嘌呤能受体介导的。检测ATP引起的胞质[Ca2+]升高以及比较几种ATP类似物增强分化的效力表明，增强分化的作用是通过M1细胞表面表达的P2y嘌呤能受体介导的。在暴露3小时内，单独的ATP略微增加了分化相关的即刻早期反应基因c-myc和JunB的表达，并且ATP还增强了IL-6诱导的这些基因的表达。ATP类似物诱导JunB表达与其增强分化的效力相关，这表明ATP诱导JunB是其发挥分化增强作用所涉及的信号通路之一。
