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Activated human blood monocytes trigger the antitumor activity of blood polymorphonuclear cells
1Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Abstract:
The purpose of these studies was to determine whether human peripheral blood polymorphonuclear cells (PMNC) can be directly activated by lymphokines or bacterial products to lyse tumorigenic cells under in vitro conditions. Preparations of PMNC with different levels of purity were isolated by countercurrent elutriation. PMNC were incubated with recombinant interferon gamma and muramyldipeptide, with lipopolysaccharide, or with the synthetic lipopeptide CGP 31362. Only PMNC preparations containing 3-5% mononuclear cells lysed allogeneic melanoma cells. Homogeneous populations of PMNC did not. The addition of 5% monocytes to homogeneous populations of PMNC triggered PMNC-mediated tumor lysis. Cell-to-cell contact was not required in this process since culture supernatant of blood monocytes incubated with lipopolysaccharide (but not with medium) could trigger tumor cell lysis by PMNC. PMNC lysed both allogeneic tumorigenic (melanoma) and allogeneic nontumorigenic (fibroblast) cells, whereas activated monocytes lysed only tumorigenic cells. In conclusion, PMNC are triggered to lyse target cells by blood monocytes activated by bacterial products or by lymphokines.
Insights
Human peripheral blood polymorphonuclear cells (PMNC) require activated monocytes to lyse tumor cells. Bacterial products or lymphokines activate monocytes, which then trigger PMNC-mediated tumor cell lysis in vitro.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human peripheral blood polymorphonuclear cells (PMNC) are key immune cells.
- Understanding PMNC activation for tumor cell lysis is crucial for immunotherapy.
Purpose of the Study:
- To investigate if PMNC can directly lyse tumorigenic cells when activated by lymphokines or bacterial products.
- To determine the role of monocytes in PMNC-mediated tumor cell lysis.
Main Methods:
- Isolation of PMNC with varying purity using countercurrent elutriation.
- Incubation of PMNC with immune activators like interferon gamma, muramyldipeptide, lipopolysaccharide, and CGP 31362.
- Co-incubation of PMNC with monocytes and assessment of tumor cell lysis.
Main Results:
- PMNC preparations with 3-5% mononuclear cells effectively lysed allogeneic melanoma cells, unlike homogeneous PMNC populations.
- Addition of 5% monocytes to PMNC triggered PMNC-mediated tumor lysis.
- Supernatant from lipopolysaccharide-activated monocytes induced tumor cell lysis by PMNC, indicating cell-cell contact is not required.
Conclusions:
- PMNC lysis of target cells is triggered by blood monocytes activated by bacterial products or lymphokines.
- Monocytes play a critical role in mediating PMNC's anti-tumor activity.