Cell Cycle Specific Effects of Tumor Necrosis Factor α in Monocyte Mediated Leukemic Cell Death and the Role of β2-Integrins

摘要: Abstract Human monocytes are involved in host defense against neoplastic cells. In view of cellular immunotherapy with cytotoxic minimal residual disease acute myeloid leukemia we have studied the role cell cycle dependent leukemic death U937, THP-1, and HL-60 cells vitro . Leukemic separated G 1 by countercurrent centrifugal elutriation were highly susceptible to monocyte mediated cytotoxicity, whereas S 2 -M less sensitive or completely resistant as compared unfractionated control became cytotoxicity upon differentiation induction 1,25-dihydroxyvitamin D 3 which paralleled an accumulation cycle. The differences susceptibility phase populations sensitivity effects tumor necrosis factor α, secreted γ-inteferon activated monocytes. Furthermore, was markedly inhibited presence anti-CD11/CD18 monoclonal antibodies recognizing α β chains -integrin adhesion proteins. By fluorescence sorter immunofluorescence a marked increase mean density -integrins could be demonstrated on unseparated A decrease shown for -M. blocking experiments antibodies, functionally relevant since most cytotoxicity. conclusion these data show that expression may play central antileukemic activity.