ABSTRACT
A protein-inhibiting LAK cell-mediated cytotoxicity was isolated from a LAK cell-conditioned medium. The N-terminal amino acid sequence of this protein appeared to be identical to fetal calf fetuin. Pure isolated fetuin, as well as commercially available preparations of this protein, were shown to inhibit cytotoxic activity of both cytotoxic proteins released by LAK cells and TNF.
Subject(s)
Killer Cells, Lymphokine-Activated/immunology , Tumor Necrosis Factor-alpha/biosynthesis , alpha-Fetoproteins/immunology , Animals , Cattle , Culture Media, Conditioned , Cytotoxicity, Immunologic , Fibroblasts , Humans , Mice , Recombinant Proteins/biosynthesis , Tumor Cells, CulturedABSTRACT
We have demonstrated that the relative contribution of secreted and membrane-associated proteins to the cytotoxicity of LAK cells depended on LAK cell phenotype: the cytotoxicity of CD16+ CD8+ CD3- LAK cells was associated mainly with membrane-bound proteins, and the activity of CD3+ CD8+ CD16- LAK cells was due mainly to secreted soluble proteins. The cytotoxic activity of membrane fractions of LAK cells against cell line L929 was determined by 40-, 32- and 21-kDa proteins for LAK cells bearing NK-specific markers and due to proteins of 34 and 21 kDa in the case of 'CTL-like' LAK-cells.
Subject(s)
Cytotoxins/physiology , Killer Cells, Lymphokine-Activated/physiology , Membrane Proteins/physiology , Animals , Electrophoresis, Polyacrylamide Gel , Humans , Immunoblotting , Immunophenotyping , L Cells/immunology , Mice , Tumor Cells, Cultured/immunologyABSTRACT
The role of necrotic and apoptotic pathways in cytolysis mediated by LAK cells was studied. The contribution of necrotic and apoptotic processes to cytolysis depends both on the LAK cells' phenotype and the type of target cells. CD16+/CD8+/CD3- LAK cells induced necrosis of K562 and L929 target cells. The cell death induced by CD3+/CD8+/CD16- LAK cells was found to include features of apoptotic and necrotic processes.
