Effect of intraperitoneal administration of granulocyte/macrophage-colony-stimulating factor in rats on omental milky-spot composition and tumoricidal activity in vivo and in vitro
Effect of intraperitoneal administration of granulocyte/macrophage-colony-stimulating factor in rats on omental milky-spot composition and tumoricidal activity in vivo and in vitro
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DOI：
10.1007/s002620050288
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发表时间：
1996-06-01
影响因子：
5.8
通讯作者：
Meijer, S
中科院分区：
文献类型：
--
作者：
Koenen, HJPM;Smit, MJ;Meijer, S
大网膜中的乳白色斑点是主要由巨噬细胞组成的白细胞的小聚集，并且最近显示为腹膜内（i. p.）接种肿瘤细胞。然而，乳斑巨噬细胞显示出杀肿瘤活性，因此可能是适合局部免疫治疗的效应细胞的极好来源。在本研究中，我们首先检查是否粒细胞/巨噬细胞集落刺激因子（GM-CSF）处理分离的乳斑巨噬细胞影响对同系结肠癌细胞（CC 531）在体外的细胞毒性。其次，我们研究了腹腔注射GM-CSF对乳斑和腹腔巨噬细胞数量和抗肿瘤活性的影响。所有研究均在Wag/Rij大鼠中进行，其中具有同基因结肠癌细胞系（CC 531）。体外研究的结果表明，GM-CSF处理网膜巨噬细胞导致对肿瘤细胞系的细胞毒性增加。连续7天每天腹腔注射1000 U GM-CSF，表明乳斑巨噬细胞的抗肿瘤活性增强，乳斑巨噬细胞群增加。增殖能力的增加，根据溴脱氧尿苷掺入，显示在乳斑巨噬细胞。考虑到腹腔注射GM-CSF治疗后巨噬细胞数量的增加及其活性的增强，乳斑巨噬细胞可能为预防腹腔内肿瘤生长的局部腹腔内免疫治疗提供了依据。
Milky spots in the greater omentum are small accumulations of leucocytes that consist mainly of macrophages and have recently shown to be a selective dissemination site of intraperitoneal (i.p.) inoculated tumour cells. However, milky-spot macrophages show tumoricidal activity and may, therefore, be an excellent source of effector cells suited for local immunotherapy. In the present study we first examined whether granulocyte/macrophage-colony-stimulating factor (GM-CSF) treatment of isolated milky-spot macrophages affects the cytotoxicity against syngeneic colon carcinoma cells (CC531) in vitro. Secondly, we studied the influence of intraperitoneal GM-CSF administration on the number and antitumour activity of milky-spot and peritoneal macrophages. All studies were performed in Wag/Rij rats in which a syngeneic colon carcinoma cell line (CC531) is available. The results of the in vitro study showed that GM-CSF treatment of the omental macrophages led to an increased cytotoxicity against the tumour cell line. Intraperitoneal administration of 1000 U GM-CSF daily for 7 consecutive days demonstrated both an enhanced antitumour activity of the milky-spot macrophages and an increase in the milky-spot macrophage population. An increase in the proliferative capacity, according to bromodeoxyuridine incorporation, was shown in the milky-spot macrophages. Taking into account both the enhanced macrophage number and their enhanced activity upon i.p. GM-CSF treatment, the milky-spot macrophages may provide a rationale for local intraperitoneal immunotherapy in the prevention of intra-abdominal tumour growth.