Lack of dynamic lipid changes after binding of interleukin 2 in chronic lymphatic leukemia lymphocytes indicates defective transmembrane signalling.
The role of membrane fluidity in the process of signal transduction after binding of Interleukin-2 (Il-2) to its specific cell-surface receptor was investigated in lymphocytes from normal donors and patients with Chronic Lymphocytic Leukemia (CLL). Membrane fluidity was assessed by fluorescence polarization analysis of the apolar fluorophor 1,6-diphenyl-1, 3, 5-hexatrien (DPH) incorporated in the lipid core of the cell membrane. Phytohemagglutinin (PHA) stimulation of lymphocytes for 72h disclosed marked membrane fluidization in normal lymphocytes without affecting lipid phase separation lacking in leukemic cells. Binding of Il-2 induced a significant decrease of the thermotropic transition temperature and overall membrane fluidization within 1h. These effects were not observed in CLL lymphocytes. Results are discussed in terms of defective transmembrane signalling in leukemic cells and pathogenetic implications for uncoupling from proliferation and differentiation signals in the development of leukemia.
Daefler
S
S
Pathology Institute, University of Cologne, F.R.G.
Krueger
G R
GR
D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D008560:Membrane Fluidity; D015375:Receptors, Interleukin-2 / Q000032:analysis; D015398:Signal Transduction; D013696:Temperature
D007376:Interleukin-2; D015375:Receptors, Interleukin-2