title: 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.
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.
authors.affiliation: Department of Cell Biology and Immunology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Koenen
authors.forename: M J
authors.initials: MJ
authors.lastname: Smit
authors.forename: M M
authors.initials: MM
authors.lastname: Simmelink
authors.forename: B
authors.initials: B
authors.lastname: Schuurman
authors.forename: R H
authors.initials: RH
authors.lastname: Beelen
authors.forename: S
authors.initials: S
authors.lastname: Meijer
mesh_terms: D000818:Animals; D002452:Cell Count; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D009852:Omentum; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor