Glycation products in aged thioglycollate medium enhance the elicitation of peritoneal macrophages
Glycation products in aged thioglycollate medium enhance the elicitation of peritoneal macrophages
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DOI：
10.1016/s0022-1759(96)00224-4
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发表时间：
1997-02-28
影响因子：
2.2
通讯作者：
Mitsuhashi, T
中科院分区：
文献类型：
--
作者：
Li, YM;Baviello, G;Mitsuhashi, T
巯基乙酸盐培养基（TGM）被广泛用作诱导小鼠和大鼠巨噬细胞的非感染性腹膜炎症的刺激剂。长期以来，人们已经知道老化的高压灭菌的TGM比新鲜制备的TGM更有效，然而，负责老化的TGM的这种增强的活性的机制仍然不清楚。TGM的老化明显有利于蛋白质和还原糖之间的非酶促反应，这可能导致晚期糖基化终产物（AGEs）的产生。我们发现老化的TGM比新鲜的TGM含有多40倍的AGEs，与AGE抑制剂氨基胍共孵育可完全阻断TGM中AGEs的形成。将老化TGM腹腔注射到大鼠体内，引起的巨噬细胞比新鲜TGM多约2倍，然而，将AGE修饰的蛋白质添加到新鲜TGM中使腹膜细胞的产量增加到显著高于新鲜和老化TGM的水平。单独注射AGE修饰的蛋白质并没有引起比常驻腹膜细胞水平显著更多的巨噬细胞。这些结果表明，AGEs的形成，在老化的TGM的巨噬细胞诱导活性增强负责。AGEs可能作为一种增强剂增强炎症反应，补充AGEs的TGM可能为诱导腹腔巨噬细胞或建立炎症动物模型提供一种有效的方法。
Thioglycollate medium (TGM) is widely used as a stimulatory agent to induce non-infectious peritoneal inflammation for elicitation of macrophages from mice and rats. It has been known for a long time that aged, autoclaved TGM is more efficient than freshly prepared TGM, however, the mechanism responsible for this enhanced activity of aged TGM remains obscure. The aging of TGM apparently favors the non-enzymatic reactions between proteins and reducing sugars in TGM that may lead to the generation of advanced glycation endproducts (AGEs). We have found that aged TGM contains 40-fold more AGEs than fresh TGM, The formation of AGEs in TGM was completely blocked by co-incubation with an AGE inhibitor, aminoguanidine. Intraperitoneal injection of aged TGM into rats elicited approximately 2-fold more macrophages than fresh TGM, However, the addition of AGE-modified proteins to fresh TGM increased the yield of peritoneal cells to a level which was significantly higher than both fresh and aged TGM. The injection of AGE-modified proteins alone did not elicit significantly more macrophages than the level of resident peritoneal cells. These results suggest that the formation of AGEs during aging of TGM is responsible for the enhanced macrophage-eliciting activity in aged TGM. AGEs may act as an enhancing agent to augment the existing inflammatory responses, AGE-supplemented TGM may provide an efficient method for eliciting peritoneal macrophages or establishing an inflammatory animal model.