Role of phorbol ester receptors in the 12-0-tetradecanoyl-phorbol-13-acetate (TPA)-induced down-regulation of colony-stimulating factor (CSF-1) binding to murine peritoneal exudate macrophages.
Role of phorbol ester receptors in the 12-0-tetradecanoyl-phorbol-13-acetate (TPA)-induced down-regulation of colony-stimulating factor (CSF-1) binding to murine peritoneal exudate macrophages.
复制标题
佛波酯受体在 12-0-十四酰佛波醇-13-乙酸酯 (TPA) 诱导的集落刺激因子 (CSF-1) 与小鼠腹膜渗出物巨噬细胞结合的下调中的作用。
DOI：
10.1002/jcp.1041240221
复制
发表时间：
1985
影响因子：
5.6
通讯作者：
Wilkins,KL
中科院分区：
文献类型：
--
作者：
Chen,BD;Wilkins,KL
Treatment of murine peritoneal exudate macrophages (PEM) by tumor‐promoting phorbol esters (TPA) results in a rapid loss of binding activity to radioactive‐labeled colony‐stimulating factor ([125I]‐CSF‐1) on the cell surface. The inhibitory effect of TPA on PEM is transient; treated cells recover full [125I]‐CSF‐1 binding activity in less than 6 hr at 37°C either in the presence or after the removal of added TPA. The role of phorbol ester receptors in the induction of [125I]‐CSF‐1 binding inhibition was studied. The biologically active ligand [3H]‐phorbol 12,13‐dibutyrate ([3H]‐PDBu) bound specifically to cultured murine PEM. At 0°C, stable and equilibrium binding occurred after 2–3 hr. Scatchard analysis revealed linear plots with a dissociation constant and receptor number per cell of 20.9 nM and 3.9 × 105/cell, respectively. Treatment of PEM with biologically active phorbol esters at 37°C rapidly inhibited the binding activity of [3‐H]‐PDBu on cell surface (down‐regulation) and rendered these cells refractory to the TPA‐induced [125I]‐CSF‐1 binding inhibition by the subsequent TPA treatment. The inhibition of phorbol ester binding activity on TPA‐treated PEM is caused by a reduction in the total number of available phorbol ester receptors rather than by a decrease in receptor affinity as judged by Scatchard analysis. The disappearance of [3H]‐PDBu binding activity is reversible and transient. However, unlike CSF‐1 receptors the restoration of phorbol ester receptors on TPA‐treated PEM is a very slow process; a prolonged incubation of up to 72 hr after the removal of TPA was required for PEM to regain fully its [3H]‐PDBu binding activity. Furthermore, the degree of TPA‐induced CSF‐1‐receptor down‐regulation is closely associated with the number of available phorbol ester receptors present on PEM at the time of treatment. Thus, the refractoriness to TPA diminished as the phorbol ester receptors on PEM recovered. A 72‐hr incubation time at 37°C was needed for PEM to lose their refractoriness and again become fully sensitive to TPA‐induced CSF‐1‐receptor down‐regulation. This study provides evidence that the loss of CSF‐1‐receptors induced by TPA treatment requires the presence of phorbol ester receptors and proceeds presumbaly via a co‐internalization of both CSF‐1 and phorbol ester receptors; the refractoriness to TPA is thereby induced by a transient loss of available phorbol ester receptors.
