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Abstract
The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (ρ = 1.080 g/ml), NS2 (ρ = 1.090 g/ml) and NS3 (1.100>ρ>1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.
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Fig. 1.
Production of suppression factors (suppressive activity) by three NS cell fractions with and without (w/o) influence of inducers. Data are shown as mean±SD.
Fig. 2.
Cytolytic activity of spleen NK cells obtained from untreated and AFP-treated mice. Data are shown as mean±SD.
Fig. 3.
Influence of a single AFP injection on Ehrlich carcinoma (EC) growth. Tumor mass was observed with and without AFP injection after EC inoculation at the 14th day. Data are shown as mean±SD.
Table 1.
Antiproliferative and NK inhibitory activity of NS cell fractions. Suppressive activity of different NS cell fractions either under influence or without (w/o) influence of AFP, which inhibits both myeloma cell proliferation (SA) and NK cytolytic activity (CLA)
| Cell targets for suppressive factors | SA/CLA, % | |||||
|---|---|---|---|---|---|---|
| NS1 | NS2 | NS3 | ||||
| w/o | AFP | w/o | AFP | w/o | AFP | |
| Myeloma | 3.8±7.7 | 50.6±1.2 | 2.4±8.1 | 52.6±1.4 | −2.5±4.7 | 43.5±2.4 |
| P (w/o) | 0.001 | 0.001 | 0.001 | |||
| P (NS3) | 0.005 | 0.002 | ||||
| NK∗ | 73.5±4.0 | 55.6±2.3 | 77.0±2.4 | 42.9±3.4 | 72.6±2.6 | 58.8±4.1 |
| P (w/o) | 0.005 | 0.001 | 0.012 | |||
| P (NS2) | 0.008 | 0.007 | ||||
Table 2.
Spontaneous or AFP-induced NS activity after EC cell inoculation or AFP injection. Suppressive activity (SA) to inhibit myeloma cell proliferation by different NS cell fractions obtained from EC bearing – or intact mice after a single AFP injection
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