Fan K, Ruan Q, Sensenbrenner L, Chen B
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48202.
Blood. 1992 Apr 1;79(7):1679-85.
Transforming growth factor-beta (TGF-beta) is a family of polypeptide growth factors with multiple functional activities. Recent studies suggest that TGF-beta is a selective inhibitor of hematopoietic cells. In this report, we study the effect of TGF-beta 1 on the proliferation of murine peritoneal exudate macrophages (PEM) in response to purified murine recombinant granulocyte-macrophage colony-stimulating factor (rMuGM-CSF) and human recombinant M-CSF (rHuM-CSF). In mice, PEM and other types of tissue macrophages display multiple types of receptors for CSFs and respond to them, either alone or in combination, to undergo extensive proliferation in vitro. Recombinant human TGF-beta 1 (rHuTGF-beta 1) (0.1 to 1.0 ng/mL) markedly enhanced the growth of PEM in response to rMuGM-CSF but inhibited their responsiveness to rHuM-CSF. Similar effects of rHuTGF-beta 1 were also detected using murine pulmonary alveolar macrophages (PAM) and bone marrow-derived macrophages (BMDM). Receptor binding assays using iodinated rMuGM-CSF and rHuM-CSF showed that rHuTGF-beta 1 treatment greatly enhanced the expression of GM-CSF receptors in PEM, in a time- and dose-dependent manner, suggesting a possible mechanism for the synergistic effect of TGF-beta 1. On the other hand, the expression of M-CSF receptors was not affected by TGF-beta 1 treatment. Analysis by mRNA PCR showed that the synergistic effect of TGF-beta 1 is not due to autocrine CSFs produced by treated cells. Our results suggest that TGF-beta 1 is an important regulator of macrophage proliferation. Depending on the types of CSFs present, TGF-beta 1 may act either as a growth promoter or inhibitor.
转化生长因子-β（TGF-β）是一类具有多种功能活性的多肽生长因子。最近的研究表明，TGF-β是造血细胞的选择性抑制剂。在本报告中，我们研究了TGF-β1对小鼠腹腔渗出巨噬细胞（PEM）增殖的影响，这些巨噬细胞对纯化的小鼠重组粒细胞-巨噬细胞集落刺激因子（rMuGM-CSF）和人重组M-CSF（rHuM-CSF）产生反应。在小鼠中，PEM和其他类型的组织巨噬细胞表现出多种CSF受体，并对它们单独或联合做出反应，从而在体外进行广泛增殖。重组人TGF-β1（rHuTGF-β1）（0.1至1.0 ng/mL）显著增强了PEM对rMuGM-CSF的生长反应，但抑制了它们对rHuM-CSF的反应性。使用小鼠肺泡巨噬细胞（PAM）和骨髓来源的巨噬细胞（BMDM）也检测到了rHuTGF-β1的类似作用。使用碘化rMuGM-CSF和rHuM-CSF进行的受体结合试验表明，rHuTGF-β1处理以时间和剂量依赖性方式极大地增强了PEM中GM-CSF受体的表达，这表明TGF-β1协同作用的一种可能机制。另一方面，M-CSF受体的表达不受TGF-β1处理的影响。mRNA PCR分析表明，TGF-β1的协同作用不是由于处理细胞产生的自分泌CSF。我们的结果表明，TGF-β1是巨噬细胞增殖的重要调节因子。根据存在的CSF类型，TGF-β1可能作为生长促进剂或抑制剂起作用。
