al-Katib A, Mohammad R M, Khan K, Dan M E, Pettit G R, Sensenbrenner L L
Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan.
J Immunother Emphasis Tumor Immunol. 1993 Jul;14(1):33-42. doi: 10.1097/00002371-199307000-00005.
We have previously reported that the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) induces further differentiation of the human acute lymphoblastic leukemia cell line Reh to a monocytoid B lymphocyte stage. In the present study, we investigated the differentiating capacity of another protein kinase C (PKC) activator, bryostatin 1 (bryo). Reh cells were treated in vitro with TPA, bryo, or interferon-alpha (IFN-alpha) for a period of 5 days during which cells were analyzed for changes in growth patterns, morphology, cytochemistry, and surface phenotype. Bryo caused a dose-dependent growth inhibition of Reh cells. Morphologically, the treated cells expressed monocytoid features with development of filopodia and numerous vacuoles indicating phagocytic activity. Bryo induced similar phenotypic changes to TPA, including induction of CD11c, increased expression of CD22 and down-regulation of CD10 and CD19. Enzymatically, bryo, like TPA, induced tartrate-sensitive acid phosphatase expression but failed to induce periodic acid Schiff (PAS) and nonspecific esterase (NSE). Bryo inhibited the TPA action on NSE and CD10. IFN-alpha showed additive growth inhibitory and phenotypic effects to bryo. Collectively, our findings indicate that bryo is capable of inducing further differentiation of the Reh cells along the B cell lineage similar to those of TPA.
我们之前报道过佛波酯12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）可诱导人急性淋巴细胞白血病细胞系Reh进一步分化至单核样B淋巴细胞阶段。在本研究中，我们研究了另一种蛋白激酶C（PKC）激活剂苔藓抑素1（bryo）的分化能力。将Reh细胞在体外分别用TPA、bryo或α - 干扰素（IFN - α）处理5天，在此期间分析细胞在生长模式、形态、细胞化学和表面表型方面的变化。Bryo对Reh细胞产生剂量依赖性生长抑制。在形态上，处理后的细胞表现出单核样特征，有丝状伪足形成和大量空泡，表明具有吞噬活性。Bryo诱导的表型变化与TPA相似，包括诱导CD11c表达、增加CD22表达以及下调CD10和CD19表达。在酶学方面，bryo与TPA一样，诱导抗酒石酸酸性磷酸酶表达，但未能诱导过碘酸希夫（PAS）反应和非特异性酯酶（NSE）。Bryo抑制TPA对NSE和CD10的作用。IFN - α对bryo的生长抑制和表型效应具有相加作用。总的来说，我们的研究结果表明，bryo能够诱导Reh细胞沿着B细胞谱系进一步分化，与TPA类似。
