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Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
Suppression of lymphokine-activated killer induction by neutrophils
Abstract:
Peripheral blood polymorphonuclear neutrophils (PMN) suppressed the induction of PBL lymphokine-activated killer (LAK) function by rIL-2 in vitro. The suppression depended on the concentration of PMN in the IL-2 culture, and required intact PMN. However, PMN did not require treatment with immunoregulators such as IL-2, LPS, or TNF to express the suppressive activity, and no direct contact with PBL was needed for the suppression. Addition of anti-TNF antibodies had no effect on the suppression, suggesting that no endogenous TNF in the culture was involved in the suppression. PMN did not inhibit LAK function by preventing utilization of IL-2 by PBL or by selective depletion of NKH-1+ cells which constitute the majority of LAK precursors in PBL. The suppression was reversed by superoxide dismutase but not by catalase, suggesting that superoxide anion, not hydrogen peroxide, was involved in the suppression. No other suppressive factor was detectable in PMN culture supernates. Our results of PMN regulating LAK induction in vitro suggest that PMN may have a role in determining the outcome of immunotherapy with IL-2 in vivo.
Insights
Peripheral blood polymorphonuclear neutrophils (PMN) inhibit lymphokine-activated killer (LAK) cell function in vitro. This suppression is mediated by superoxide anions and suggests a role for PMN in interleukin-2 (IL-2) immunotherapy outcomes.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Interleukin-2 (IL-2) therapy enhances lymphokine-activated killer (LAK) cell activity for cancer treatment.
- The role of polymorphonuclear neutrophils (PMN) in modulating LAK cell function is not fully understood.
Purpose of the Study:
- To investigate the effect of peripheral blood polymorphonuclear neutrophils (PMN) on the induction of LAK cell function by IL-2 in vitro.
- To elucidate the mechanism by which PMN suppress LAK cell induction.
Main Methods:
- Co-culture of peripheral blood lymphocytes (PBL) with varying concentrations of intact PMN in the presence of recombinant IL-2 (rIL-2).
- Assessment of LAK cell function and analysis of suppressive mechanisms, including the role of reactive oxygen species and cell contact.
- Treatment with superoxide dismutase (SOD) and catalase to identify the suppressive factor.
Main Results:
- PMN significantly suppressed IL-2-induced LAK cell function in a dose-dependent manner.
- Suppression required intact PMN but not direct cell-to-cell contact or prior activation with immunoregulators.
- The suppressive effect was reversed by SOD, indicating involvement of superoxide anion, but not by catalase.
- PMN did not inhibit IL-2 utilization or deplete LAK precursor cells.
Conclusions:
- Peripheral blood PMN possess a potent inhibitory effect on LAK cell induction by IL-2 in vitro.
- Superoxide anion production by PMN is the likely mediator of this suppression.
- These findings suggest that PMN may influence the efficacy of IL-2-based immunotherapy in vivo.
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