Urieli-Shoval S, Meek R L, Hanson R H, Eriksen N, Benditt E P
Department of Pathology, University of Washington, Seattle 98195.
Am J Pathol. 1994 Sep;145(3):650-60.
Serum amyloid A (apoSAA) is a family of proteins found, mainly associated with high density lipoproteins, in the blood plasma of mammals and at least one avian species, the Pekin duck. These proteins are present in small amounts under normal circumstances, but their concentration is capable of rising 100- to 1,000-fold in situations involving tissue injury or infection. Like classic acute phase proteins they are produced in the liver; however, expression of one of the apoSAA genes is known to occur in activated macrophages of mice. We examined three human macrophage precursor cell lines (THP-1, U-937, and HL-60), before and after differentiation with phorbol 12-myristate 13-acetate or 1 alpha,25-dihydroxy-vitamin D3, for apoSAA messenger (m)-RNA expression and found that: 1) induction of steady-state apoSAA mRNA by lipopolysaccharide, interleukin-1, or interleukin-6 required the presence of the synthetic glucocorticoid dexamethasone; 2) the three known active genes, apoSAA1, apoSAA2, and apoSAA4, were induced in THP-1 cells, whereas the pseudogene apoSAA3 was not; 3) differentiated and undifferentiated THP-1 cells expressed apoSAA mRNA, but U-937 cells expressed apoSAA mRNA (low levels) only after phorbol 12-myristate 13-acetate differentiation and HL-60 cells did not express apoSAA mRNA whether differentiated or not; 4) apoSAA protein was detectable immunologically at a low level in lyophilized medium from induced THP-1 cells. Our findings are compatible with the hypotheses that 1) apoSAA gene expression in human monocytes/macrophages in vivo is differentiation dependent; 2) activated macrophages provide a local source of apoSAA at sites of tissue injury or inflammation; 3) apoSAA is induced in tissue macrophages by local stimuli, under conditions that may not evoke the systemic acute phase response.
血清淀粉样蛋白A（载脂蛋白SAA）是一类蛋白质，主要与高密度脂蛋白相关，存在于哺乳动物以及至少一种鸟类（北京鸭）的血浆中。在正常情况下，这些蛋白质含量很少，但在组织损伤或感染时，其浓度能够升高100至1000倍。与经典急性期蛋白一样，它们在肝脏中产生；然而，已知载脂蛋白SAA基因之一在小鼠活化巨噬细胞中表达。我们检测了三种人巨噬细胞前体细胞系（THP-1、U-937和HL-60）在用佛波酯12-肉豆蔻酸酯13-乙酸酯或1α,25-二羟基维生素D3分化前后的载脂蛋白SAA信使核糖核酸（m）-RNA表达，发现：1）脂多糖、白细胞介素-1或白细胞介素-6诱导稳态载脂蛋白SAA mRNA需要合成糖皮质激素地塞米松的存在；2）三个已知的活性基因，载脂蛋白SAA1、载脂蛋白SAA2和载脂蛋白SAA4在THP-1细胞中被诱导，而假基因载脂蛋白SAA3未被诱导；3）分化和未分化的THP-1细胞表达载脂蛋白SAA mRNA，但U-937细胞仅在佛波酯12-肉豆蔻酸酯13-乙酸酯分化后表达载脂蛋白SAA mRNA（低水平），HL-60细胞无论是否分化均不表达载脂蛋白SAA mRNA；4）在诱导的THP-1细胞的冻干培养基中可通过免疫检测到低水平的载脂蛋白SAA蛋白。我们的发现与以下假设相符：1）体内人单核细胞/巨噬细胞中的载脂蛋白SAA基因表达依赖于分化；2）活化巨噬细胞在组织损伤或炎症部位提供载脂蛋白SAA的局部来源；3）在可能不会引发全身急性期反应的条件下，局部刺激可诱导组织巨噬细胞中的载脂蛋白SAA。
