Comparative susceptibility of peripheral blood leucocytes and related cell lines to killing by T-cell perforin.
The comparative susceptibility of lymphocyte subsets, monocytes and polymorphonuclear leucocytes (PMN) to killing by murine perforin was measured using physical separation techniques, cell-surface phenotyping and scatter characteristics to isolate cell types, together with propidium iodide (PI) uptake as a measure of cell death. In the majority of individuals, PMN were more resistant to perforin than other peripheral blood cells including natural killer (NK) cells and CD8+ lymphocytes. Among the lymphocytes, CD4+ cells were the most susceptible subset, followed by CD19+, CD8+ and CD56+ lymphocytes respectively. The human promyelocytic leukaemia cell line, HL-60, and the human histiocytic lymphoma cell line, U937, were readily killed by perforin. When HL-60 were differentiated to either macrophage- or neutrophil-like end cells, and U937 differentiated to macrophage-like end cells, there was no difference between differentiated and undifferentiated cells in their relative susceptibility to perforin. The relative resistance of PMN to perforin may be important in protecting them from damage in in vivo situations where both NK cells and neutrophils are localized in the same inflammatory areas.
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, U.K.
J
J
Jones
B P
BP
Morgan
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D016131:Lymphocyte Subsets / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin