The signal pathway for control of apoptosis in human neutrophils is currently unknown. In this study, we provide the first evidence that a Src family tyrosine kinase, Lyn, plays a key role in inhibition polymorphonuclear (PMN) cell death. Several nuclear proteins associated with apoptosis, i.e., p53, cdc2, and Rb, were absent from PMN. Bcl-2, known to inhibit apoptosis, was also not expressed. Programmed cell death that rapidly occurred in PMN could be arrested by granulocyte-macrophage CSF (GM-CSF), but this activation did not induce p53, cdc2, retinoblastoma, or Bcl-2 expression. Instead, GM-CSF produced a rapid activation of Lyn and Hck, but not Fgr, tyrosine phosphorylation within 1 min. Co-immunoprecipitation studies indicated that only Lyn, but not Hck, was physically coupled to GM-CSF receptor. By histologic assessment and evaluation of DNA fragmentation, only antisense Lyn, but not antisense Hck or antisense Fgr, could reverse the cell survival advantage provided by GM-CSF. Therefore, the physical coupling of Lyn to GM-CSF receptor and its early activation are required for inhibition or delay of apoptosis in PMN.
CITATION STYLE
Wei, S., Liu, J. H., Epling-Burnette, P. K., Gamero, A. M., Ussery, D., Pearson, E. W., … Djeu, J. Y. (1996). Critical role of Lyn kinase in inhibition of neutrophil apoptosis by granulocyte-macrophage colony-stimulating factor. The Journal of Immunology, 157(11), 5155–5162. https://doi.org/10.4049/jimmunol.157.11.5155
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