Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration
Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration
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DOI：
10.1007/s00441-004-0987-2
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发表时间：
2004-12-01
影响因子：
3.6
通讯作者：
Seelaender, MCL
中科院分区：
文献类型：
--
作者：
Machado, AP;Rosa, LFPBC;Seelaender, MCL
脂肪组织(AT)受到恶病质的严重影响，这是一种副肿瘤综合征，增加了癌症的发病率和死亡率。然而，根据AT仓库的说法，对这种情况的反应是不同的。由于血浆瘦素浓度在恶病质中的变化经常被报道，我们用物种特异性放射免疫法测定了Walker 256荷瘤大鼠的腹膜后(RPAT)、附睾部(EAT)和肠系膜(MES)三个AT部位的瘦素浓度。从注射肿瘤细胞后的第4天起，恶病质大鼠的所有血库和血浆中的瘦素浓度就降低了(P<；0.0001)。在所有从荷瘤动物获得的AT中观察到细胞浸润物的存在。超微结构分析、rt1B免疫细胞化学(表明存在MHCII)和抗单核巨噬细胞抗体显示，这些细胞是巨噬细胞。研究渗出液分泌肿瘤坏死因子α和前列腺素E(2)的情况(商业试剂盒)。与恶病质大鼠的腹膜巨噬细胞相比，ALL AT(P<；0.05)的巨噬细胞分泌这两种因子的量增加，而MES的巨噬细胞分泌的肿瘤坏死因子α的量最高。结果提示，慢性局部产生的肿瘤坏死因子α和前列腺素E(2)对恶病质大鼠瘦素合成可能有调节作用。
The adipose tissue (AT) is severely affected by cachexia, a paraneoplastic syndrome, which increases the morbidity and mortality of cancer. There is, however, a heterogeneous response to the condition, according to the AT depot. As plasma leptin concentration has been often reported to vary in cachexia, we have measured ( species specific radioimmunoassay) the local concentration of leptin in three AT depots: retroperitoneal (RPAT), epididymal (EAT) and mesenteric (MES) of Walker 256 tumour-bearing rats. A reduced concentration of leptin (P< 0.0001) was found in all the depots and in the plasma of the cachectic rats, compared with controls already from day 4 after tumour cell injection. The presence of a cell infiltrate was observed in all AT obtained from the tumour-bearing animals. Ultrastructural analysis, along with immunocytochemistry for RT1B (indicating the presence of MHCII) and using antibody against mononuclear phagocytes, showed the cells to be macrophages. The profile of TNF alpha and PGE(2) secretion by the infiltrate was investigated ( commercial kits). There was increased production of both factors by the cells of all AT ( P< 0.05) compared with peritoneal macrophages obtained from the cachectic rats, while the cells isolated from MES showed the highest synthesis of TNFalpha. The results suggest a possible modulation of the chronic locally produced TNFalpha and PGE(2) upon leptin synthesis by the AT of the cachectic rats.