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Increase in liver-associated natural killer activity by polyribonucleotides.
T A Twilley1, L Mason, J E Talmadge
1Laboratory of Experimental Immunology, NCI-FCRF, Frederick, Md.
Natural Immunity and Cell Growth Regulation
|January 1, 1987
Summary
Polyinosinic-polycytidylic acid (poly ICLC) and polyadenosinic-polyuridylic acid (poly AU) significantly boost natural killer (NK) cell activity in mouse livers. This enhancement of immune response in the liver may have implications for cancer metastasis treatment.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Polyribonucleotides are investigated for cancer and viral disease treatments.
- Natural killer (NK) cell activity is crucial for immune surveillance.
- The liver is a common site for cancer metastasis.
Purpose of the Study:
- To investigate the effect of polyinosinic-polycytidylic acid (poly ICLC) and polyadenosinic-polyuridylic acid (poly AU) on natural killer (NK) cell activity in mice.
- To determine the distribution and duration of NK cell activity augmentation in different organs.
- To identify the immune cell populations responsible for the enhanced NK activity in the liver.
Main Methods:
- Administration of poly ICLC and poly AU to mice.
- Measurement of NK activity in liver, blood, and spleen using lytic units (LU).
- Isolation and characterization of liver-associated leukocytes (nonparenchymal cells, NPC) using Percoll density gradients.
- Identification of NK-mediating cells as large granular lymphocytes (LGL).
Main Results:
- Poly ICLC potently augmented NK activity in the liver (445 LU) compared to blood (63 LU) and spleen (20 LU).
- Elevated liver NK activity was sustained for at least 9 days post-poly ICLC injection.
- Poly ICLC increased liver-associated nonparenchymal cells (NPC), primarily large granular lymphocytes (LGL), which mediated the enhanced NK activity.
- Repeated administration of poly ICLC led to higher levels of liver-associated NK activity and LGL compared to a single injection.
Conclusions:
- Poly ICLC and poly AU effectively augment NK cell activity, particularly in the liver.
- The liver-associated NK activity is mediated by large granular lymphocytes (LGL) within the nonparenchymal cell population.
- Repeated poly ICLC administration enhances liver NK activity and LGL levels, suggesting potential therapeutic applications in managing cancer metastasis.