Rat Liver Arginase Suppresses Mixed Lymphocyte Reaction

An inhibitory factor to mixed lymphocyte reaction (MLR) was purified from the supernatant of rat liver homogenate by procedures including chloroform treatment, ammonium sulfate precipitation, ion-exchange column chromatography, and gel filtration. The molecular weight of the purified inhibitor was 34,000 on SDS-PAGE. We determined the amino acid sequence of the N-terminal region of the purified inhibitor to be Glu-Glu-Pro-Trp-Met-Ser-Met-Ser-Ser-Lys-Pro-Lys-Pro-Ile-Glu-. This sequence shows a high homology to a rat arginase, the amino acid sequence of which was predicted from the nucleic acid sequence of cloned rat arginase cDNA. The amino acid sequence of the purified arginase is 6 amino acid residues longer than the predicted one. The purified MLR inhibitor showed a high arginase activity. The inhibition mechanism was studied and it was discovered that L-arginine was depleted in the culture medium, and that the supply of L-arginine to the cell culture caused recovery of the incorporation of tritium thymidine. Here we present evidence that the MLR inhibitor from rat liver homogenate is the liver arginase. It is noteworthy that immune response may be controlled by a liver factor.