Human lymphokine-activated killer (LAK) cells--II. Studies of various L-amino acid methyl esters on LAK generation at high cell density.
Nineteen L-amino acid methyl esters were studied for their cytotoxic activity on human monocytes, NK activity, and LAK activation by IL-2 at high cell density (5 x 10(6) cells/ml). Phenylalanine, Met, Trp, Cys, Tyr, Asp and Glu methyl esters depleted monocytes from PBMC, caused inhibition of NK activity, and allowed LAK activation at high cell density. Alanine, Val and Pro methyl esters were marginal. Glycine, Ser, Thr, Lys, His and Arg were not active. Leucine, Ile and cystine methyl esters depleted monocytes and also NK activity; LAK activation was suppressed. The D series of the active L-amino acid (Met, Tyr and Trp) methyl esters were not active. The position of the methyl ester is important as shown by 5-Glu methyl ester which was not active as Glu(OMe)2. Phenylalanine T-butyl ester was not as active as the methyl or the ethyl ester. This indicates that the breakage of the ester bond is the rate-limiting step for the actions of the Phe alkyl esters. Seven L-amino acid amides (Ile, Leu, Phe, Val, Glu, Asp and Tyr) were studied and only Ile, Leu and Phe were found to be active. Isoleucine and Leu amides depleted monocytes with little inhibitory effect on NK activity and thus allowed LAK activation. In summary, depletion of monocytes by the amino acid methyl esters and the amides allowed LAK activation at high cell density.
Leung
K H
KH
E.I. du Pont de Nemours and Co., Medical Products Department, Glenolden Laboratory, PA 19036.
D000596:Amino Acids / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D004952:Esters; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008213:Lymphocyte Activation; D008745:Methylation; D009000:Monocytes / Q000187:drug effects
D000596:Amino Acids; D004952:Esters