Abstract
We studied the effect of recombinant murine granulocyte–macrophage colony-stimulating factor(rmGM-CSF) on the cytotoxic potential of murine peritoneal cells. Mice received rmGM-CSF intraperitoneally using different dosages and injection schemes. At different time points after the last injection, mice were sacrificed, peritoneal cells isolated and their tumour cytotoxicity was determined by a cytotoxicity assay using syngeneic [methyl-3H]thymidine-labelled colon carcinoma cells. Also, the cytotoxic response to a subsequent in vitro stimulation with lipopolysaccharide was determined. Upon daily injection of 6000–54 000 U rmGM-CSF over a 6-day period, the number of peritoneal cells increased over ten fold with the highest rmGM-CSF dose. Increases in cell numbers was mainly due to increases in macrophage numbers. Upon injection of three doses of 3000 U rmGM-CSF per day for 3 consecutive days, the number of macrophages remained elevated for minimally 6 days. Although the peritoneal cells from rmGM-CSF-treated mice were not activated to a tumoricidal state, they could be activated to high levels of cytotoxicity with an additional in vitro stimulation of lipopolysaccharide. Resident cells isolated from control mice could be activated only to low levels of tumour cytotoxicity with lipopolysaccharide. Tumour cytotoxicity strongly correlated with nitric oxide secretion. When inhibiting nitric oxide synthase, tumour cell lysis decreased. Thus, the expanded peritoneal cell population induced by multiple injections of rmGM-CSF has a strong tumour cytotoxic potential and might provide a favourable condition for immunotherapeutic treatment of peritoneal neoplasms. © 1999 Cancer Research Campaign
Highlights
Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a 20- to 30-kDa glycoprotein
We show that newly recruited macrophages, due to GM-CSF administration i.p., have high cytotoxic capacity and are able to produce large amounts of nitric oxide when activated with lipopolysaccharide (LPS)
We examined the effect of i.p. injections of recombinant murine granulocyte–macrophage colony-stimulating factor on the tumour cytotoxic properties of peritoneal cells
Summary
Granulocyte–macrophage colony-stimulating factor (GM-CSF) is a 20- to 30-kDa glycoprotein. GM-CSF administration, i.v. as well as i.p., results in an increase in circulating neutrophils, eosinophils, monocytes and all progenitor cells and in an increase in numbers and activation status of tissue macrophages (Metcalf et al, 1987; Pojda et al, 1989; Ulich et al, 1990; Selgas et al, 1996), recently reported in a human study in which GM-CSF was given i.p. to dialysis patients. They showed that intraperitoneal GM-CSF caused a marked and transient recruitment of primed macrophages into the peritoneum without causing major side-effects (Selgas et al, 1996). Intraperitoneal injections of GM-CSF could be an efficient way to activate peritoneal cells, which mainly
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
