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Neutrophil Extracellular Traps Generated by Low Density Neutrophils Obtained from Peritoneal Lavage Fluid Mediate Tumor Cell Growth and Attachment
Published on: August 3, 2018
Effect of intraperitoneal neutrophils induced by OK432 on malignant ascites
Yoshinori Hosoya1, Eiji Kobayashi, Toshihiro Takizawa
1Department of Surgery, Jichi Medical School, 3311-1 Minamikawachi, Tochigi, 329-0498, Japan.
Purpose:
To evaluate the efficacy of a streptococcal preparation, OK432, on malignant ascites in mice.
Methods:
PC-C203U (PC203) is a preparation of another strain of the streptococcal family, with the lowest antineoplastic action. To examine the survival curves of mice after the inoculation of BAMC-1 tumor cells, we gave intraperitoneal OK432, PC203, or saline as a control. Intraperitonal neutrophils were counted by cytospin, and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1alpha were measured by enzyme-linked immunosorbent assay, and 8 h after the administration of OK432, PC203, and saline. Using electron microscopy, we examined the greater omental milky spots, where the in situ proliferation of neutrophils or macrophages takes place.
Results:
The OK432 group had the best survival and the control group the worst. The ratio of intraperitoneal neutrophils to BAMC-1 was highest in the OK432 group and lowest in the control group. Quantitative IL-1beta, IL-6 and MIP-1alpha levels were correlated closely with survival. Electron microscopic examination of the milky spots revealed massive proliferation of neutrophils in the OK432 group, but not in the PC203 or control groups.
Conclusion:
OK432 effectively activated intraperitoneal neutrophils and a series of immunological chain reactions through an increase in IL-1beta, IL-6, and MIP-1alpha levels. Milky spots could have important antitumor effects in terms of the spread of neutrophils.
Insights
The streptococcal preparation OK432 significantly improved survival in mice with malignant ascites by boosting neutrophils and immune responses. This study highlights OK432
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Malignant ascites poses a significant challenge in cancer treatment.
- Streptococcal preparations are being investigated for their immunomodulatory and anti-tumor properties.
Purpose of the Study:
- To evaluate the efficacy of the streptococcal preparation OK432 in treating malignant ascites in a mouse model.
- To investigate the immunological mechanisms underlying OK432's anti-tumor effects.
Main Methods:
- Mice bearing BAMC-1 tumor cells were treated with intraperitoneal injections of OK432, PC203 (another streptococcal strain), or saline.
- Survival rates were monitored, and intraperitoneal neutrophils were quantified.
- Levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1alpha were measured via ELISA.
- Greater omental milky spots were examined using electron microscopy.
Main Results:
- OK432 treatment resulted in significantly improved survival rates compared to the control group.
- A higher ratio of intraperitoneal neutrophils to BAMC-1 tumor cells was observed in the OK432 group.
- Elevated levels of IL-1beta, IL-6, and MIP-1alpha correlated with enhanced survival.
- Electron microscopy revealed massive neutrophil proliferation within the milky spots in OK432-treated mice.
Conclusions:
- OK432 effectively activates intraperitoneal neutrophils, initiating immune responses that contribute to anti-tumor effects.
- Increased levels of IL-1beta, IL-6, and MIP-1alpha are key mediators of OK432's efficacy.
- The greater omental milky spots play a crucial role in neutrophil-mediated anti-tumor activity.

