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Participation of polymorphonuclear leukocyte-derived factor in murine tumour cell killing
Abstract:
Previous studies showed that murine polymorphonuclear leukocytes (PMNs) lyze tumour cells in the presence of wheat germ agglutinin or actinomycin D. This paper reports studies on whether a soluble factor participates in PMN-mediated cytolysis dependent on lectin or a chemotherapeutic drug. Tumour lysis was observed with supernatants from PMN cocultured with wheat germ agglutinin or actinomycin D. The supernatant from cultures of PMNs alone was not cytotoxic, but addition of these agents to the supernatant induced tumour lysis. PMNs released a soluble factor spontaneously into the medium and cytolysis was induced by a combination of this factor and wheat germ agglutinin or actinomycin D. This factor was not an oxygen metabolite, but a protein with a molecular weight of approximately 100 K daltons. These results suggest that a soluble factor(s) from PMNs participates in tumour killing in cooperation with appropriate reagents.
Insights
Murine polymorphonuclear leukocytes (PMNs) release a soluble protein factor that, with wheat germ agglutinin or actinomycin D, induces tumor cell lysis. This protein, not an oxygen metabolite, is key to PMN-mediated tumor killing.
Area of Science:
- Immunology
- Biochemistry
Background:
- Murine polymorphonuclear leukocytes (PMNs) are known to lyse tumor cells when treated with wheat germ agglutinin (WGA) or actinomycin D.
- The precise mechanism of PMN-mediated tumor cell lysis in the presence of these agents remains incompletely understood.
Purpose of the Study:
- To investigate the potential involvement of a soluble factor released by PMNs in mediating tumor cell lysis.
- To determine if this soluble factor cooperates with WGA or actinomycin D to induce cytolysis.
Main Methods:
- PMNs were cultured with or without WGA or actinomycin D.
- Supernatants from these cultures were collected and applied to tumor cells.
- The cytotoxic activity of the supernatants was assessed.
- Characterization of the soluble factor was performed, including assessment of its nature (oxygen metabolite or protein) and molecular weight.
Main Results:
- Supernatants from PMNs co-cultured with WGA or actinomycin D induced significant tumor cell lysis.
- Supernatants from PMNs cultured alone showed no cytotoxicity.
- Addition of WGA or actinomycin D to the supernatant from PMN cultures induced tumor lysis, indicating a synergistic effect.
- PMNs spontaneously released a soluble factor into the medium.
- This factor was identified as a protein with an approximate molecular weight of 100 K daltons and was not an oxygen metabolite.
Conclusions:
- A soluble protein factor released by PMNs plays a crucial role in tumor cell killing.
- This factor acts in cooperation with reagents like WGA or actinomycin D to mediate cytolysis.
- The findings suggest a novel mechanism for PMN-mediated anti-tumor activity involving secreted proteins.