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Enhancement of polymorphonuclear leukocyte-mediated tumor cytotoxicity by serum factor(s)
Abstract:
It has been reported that beta-1,3-D-glucan isolated from Alcaligenes faecalis (TAK) promoted tumor cytolysis by mouse polymorphonuclear leukocytes (PMN). We investigated the effect of serum on mouse PMN tumor cytolysis induced by TAK and other PMN stimulators. Addition of fetal calf serum (FCS) to the cytolysis assay enhanced tumor cytolysis by PMN in a dose-dependent manner. Sera obtained from horses, mice, and rats were also effective enhancers of PMN tumor cytolysis. When FCS was added after the assay was under way, the enhancing effect decreased proportionally to the time elapsed. The enhancing activity was detected over a broad range of fractions with a peak at 170 kD by fractionation on a Superose 6 column. The responsible factor(s) in serum was stable after treatment at 60 degrees C, 30 min or after lowering the pH to 2. Mouse PMN stimulated with TAK increased production of hydrogen peroxide in the presence of FCS.
Insights
Fetal calf serum enhances tumor cell killing by mouse polymorphonuclear leukocytes (PMN) when stimulated by beta-1,3-D-glucan (TAK). This serum factor is heat-stable and active in various animal sera, boosting PMN
Area of Science:
- Immunology
- Biochemistry
Background:
- Beta-1,3-D-glucan from Alcaligenes faecalis (TAK) is known to promote tumor cytolysis via mouse polymorphonuclear leukocytes (PMN).
- The role of serum factors in modulating this PMN-mediated tumoricidal activity requires further investigation.
Purpose of the Study:
- To investigate the effect of serum on mouse PMN-mediated tumor cytolysis induced by TAK.
- To characterize the serum-derived factors responsible for enhancing PMN tumoricidal activity.
Main Methods:
- Tumor cytolysis assays using mouse PMN and TAK, with varying concentrations of fetal calf serum (FCS).
- Fractionation of serum components using Superose 6 chromatography.
- Stability assays of serum factors under heat and low pH conditions.
- Measurement of hydrogen peroxide production by PMN.
Main Results:
- Fetal calf serum significantly enhanced PMN-mediated tumor cytolysis in a dose-dependent manner.
- Serum from various species (horse, mouse, rat) also demonstrated enhancing activity.
- The enhancing factor was found to be heat-stable (60°C, 30 min) and stable at low pH (pH 2), with a peak activity around 170 kD.
- TAK-stimulated mouse PMN showed increased hydrogen peroxide production in the presence of FCS.
Conclusions:
- Serum contains factors that potentiate beta-1,3-D-glucan-induced tumor cytolysis by mouse PMN.
- These serum factors are robust, suggesting potential therapeutic applications in cancer immunotherapy.
- Further characterization of these factors could lead to novel strategies for enhancing anti-tumor immune responses.