Iwabuchi Haruko, Kawasaki Takashi, Yamamoto Takashi, Uchiyama Makoto, Nakata Koh, Naito Makoto
Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan.
Cell Tissue Res. 2007 Jul;329(1):71-9. doi: 10.1007/s00441-007-0405-7. Epub 2007 Apr 4.
PU.1, which is a transcription factor, promotes the terminal differentiation of alveolar macrophages (AMs). Its expression is regulated by granulocyte/macrophage colony-stimulating factor (GM-CSF). In this study of AMs in newborn rats, we performed immunohistochemical staining, acid phosphatase staining, reverse transcriptase polymerase chain reaction (RT-PCR), quantitative real-time PCR, cytokine assay, and electron microscopy. AMs at 3 and 7 days after birth had a large foamy appearance with an intracytoplasmic accumulation of surfactants. Weak expression of PU.1 was observed in the nuclei. AMs at 15 days after birth were smaller, and PU.1 expression had increased. Ultrastructurally, AMs at 1 day after birth had a smooth surface and abundant lamellar structures in the cytoplasm, whereas AMs at 56 days after birth were characterized by (1) abundant microvillar projections on the cell surface, and (2) well-developed lysosomes and a few lamellar structures in the cytoplasm. Acid phosphatase activity and the expression of mannose receptor, scavenger receptor, and GM-CSF receptor alpha were enhanced in AMs with time after birth. These results suggest that AMs are initially immature, and that their terminal differentiation starts after birth concomitantly with an increased expression of PU.1.
PU.1是一种转录因子，可促进肺泡巨噬细胞（AM）的终末分化。其表达受粒细胞/巨噬细胞集落刺激因子（GM-CSF）调控。在这项对新生大鼠AM的研究中，我们进行了免疫组织化学染色、酸性磷酸酶染色、逆转录聚合酶链反应（RT-PCR）、定量实时PCR、细胞因子检测及电子显微镜检查。出生后3天和7天的AM呈现出大的泡沫样外观，胞质内有表面活性剂蓄积。在细胞核中观察到PU.1的弱表达。出生后15天的AM较小，且PU.1表达增加。超微结构上，出生后1天的AM表面光滑，胞质内有丰富的板层结构，而出生后56天的AM特征为：（1）细胞表面有丰富的微绒毛突起，（2）胞质内有发育良好的溶酶体和少量板层结构。出生后随着时间推移，AM的酸性磷酸酶活性以及甘露糖受体、清道夫受体和GM-CSF受体α的表达增强。这些结果表明，AM最初是不成熟的，其终末分化在出生后随着PU.1表达增加而开始。
