A 36-kilodalton tumor-derived factor with myeloid immunomodulatory activity.
The conditioned medium from the epidermal carcinoma cell line A431 is shown to inhibit the growth of three human myeloid leukemic cell lines. We have purified to homogeneity from this conditioned medium a 36-kDa protein, as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which inhibits [3H]thymidine incorporation into the DNA and induces cell surface expression of CD11b, the alpha chain of the adhesion receptor MAC-1, on the human promyelocytic leukemic cell line HL-60. This factor was purified by sequential anion exchange, hydrophobic interaction, and gel permeation chromatography. Amino acid sequence analysis of two tryptic fragments of the purified material showed greater than 95% homology with sequences 179-194 and 319-328 of the M chain of human L-lactate dehydrogenase. Although the tetrameric L-lactate dehydrogenase alone exhibits no activities associated with the purified 36-kDa protein, brief acid treatment which has been shown to yield predominantly monomeric lactate dehydrogenase-M1 results in about 50% of the maximal antiproliferative activity of that induced by this factor. The role of soluble factors of tumor origin in modulating myeloid function as part of an immunosurveillance network is discussed.
Packard
B Z
BZ
Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland 20892.
Komoriya
A
A
D000595:Amino Acid Sequence; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000276:immunology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007770:L-Lactate Dehydrogenase