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Enhancement of polymorphonuclear leukocyte (PMN) function by OK-432
E Ueta1, M Umazume, T Yamamoto
1Department of Oral Surgery, Kochi Medical School, Japan.
Abstract:
The influence of OK-432, a streptococcal preparation, on human polymorphonuclear leukocytes (PMN) was examined. OK-432 increased O2- generation was also observed when PMN were cultured with 10(-2)KE/ml OK-432 for 1 h and then stimulated with phorbol myristate acetate or formyl-metionyl-leucil-phenylalanine (FMLP). In addition, PMN O2- generation was promoted by culture supernatants of peripheral blood mononuclear cells (PBMC) incubated with 10(-3) or 10(-2) KE/ml OK-432. Furthermore, OK-432 (10(-3)-10(-2) KE/ml) enhanced the chemiluminescence of FMLP- and PMA-stimulated PMN. However, nitroblue tetrazolium reduction and myeloperoxidase activity were only minimally enhanced. Not only the candidacidal activity of PMN but also antibody-dependent cell-mediated cytotoxicity against Candida and Raji cells were enhanced in correspondence with the increased generation of reactive oxygen species. Culture of PMN or PBMC for 24 h with OK-432 resulted in a concentration-dependent increase in the substantial production of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. OK-432 also enhanced granulocyte-macrophage colony stimulating factor and gamma-interferon generation by leukocytes in a dose-dependent manner. Our research indicates that OK-432 enhances PMN function directly as well as via the promotion of cytokine production, and suggests that these effects of OK-432 could be beneficial in immunosuppressed patients.
Insights
OK-432, a streptococcal preparation, boosts human polymorphonuclear leukocyte (PMN) function by increasing reactive oxygen species and cytokine production. These effects may benefit immunosuppressed patients by enhancing immune responses.
Area of Science:
- Immunology
- Microbiology
Background:
- Polymorphonuclear leukocytes (PMN) are crucial immune cells.
- OK-432 is a streptococcal preparation with immunomodulatory potential.
Purpose of the Study:
- To investigate the effects of OK-432 on human PMN function.
- To determine if OK-432 influences cytokine production by leukocytes.
Main Methods:
- Human PMN and peripheral blood mononuclear cells (PBMC) were cultured with OK-432.
- Assays included reactive oxygen species generation, chemiluminescence, nitroblue tetrazolium reduction, myeloperoxidase activity, and cytokine quantification (IL-1β, IL-6, TNF-α, GM-CSF, IFN-γ).
- Cellular activities like candidacidal activity and antibody-dependent cell-mediated cytotoxicity were assessed.
Main Results:
- OK-432 enhanced O2- generation and chemiluminescence in PMN stimulated with phorbol myristate acetate (PMA) or formyl-metionyl-leucil-phenylalanine (FMLP).
- PMN O2- generation was also promoted by PBMC supernatants from OK-432-treated cells.
- OK-432 significantly increased the production of IL-1β, IL-6, TNF-α, GM-CSF, and IFN-γ by leukocytes in a dose-dependent manner.
- Enhanced candidacidal activity and antibody-dependent cell-mediated cytotoxicity were observed.
Conclusions:
- OK-432 directly enhances PMN function, including reactive oxygen species generation and cytotoxic activities.
- OK-432 promotes the production of key cytokines and growth factors by leukocytes.
- These immunomodulatory effects suggest potential therapeutic benefits of OK-432 for immunosuppressed patients.
