E receptor-related immunosuppressive factor in malignant pleural fluid and plasma: molecular mechanism of action on DNA-polymerase-alpha.

We previously purified a potent serum suppressor factor from malignant ascites fluid and showed that it had serologic cross-reactivity with E receptor of human T lymphocytes. We termed this factor "suppressive E receptor factor" (SER). Subsequent studies on SER showed that SER interfered with the production of interleukin 1 and 2 as well as interfering with their activities on target cells. However, SER was not directly cytotoxic to lymphocytes. In this study, we compared the inhibitor of DNA-polymerase (IDP) activity with the suppressive activity on phytohemagglutinin-induced DNA synthesis on intact cells. These two activities were closely correlated (with a linear correlation coefficient of 0.988) even with the whole plasmas derived from cancer patients. Fractionation and purification of IDP activity identified it with SER of a similar potency. Therefore, SER appeared to exhibit its potent immunosuppressive effect via its direct interference on DNA-polymerase activity. Furthermore, the DNA-polymerase inhibitory activity of SER appeared to be specific to DNA and it did not affect the RNA-polymerase activity. SER inhibition of DNA polymerase activity with respect to DNA primer as well as with the nucleotide substrate. Direct inhibition on DNA-polymerase-alpha activity may be one of the possible mechanisms of action of SER on lymphocyte proliferation.