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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Authors: | H J P M Koenen Marjon J Smit Marleen M J A Simmelink Bart Schuurman Robert H J Beelen Sybren Meijer |
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Institution: | (1) Department of Cell Biology and Immunology, Medical Faculty, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands Fax: +31 20 4448081, NL;(2) Academic Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands, NL |
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Abstract: | 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.
Received: 11 April 1996 / Accepted: 21 May 1996 |
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Keywords: | GM-CSF Intraperitoneal immunotherapy Macrophage Milky spot CC531 |
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