MAP kinase upregulation after hematopoietic differentiation: role of chemotaxis.
Mitogen-activated protein kinase (MAPK) isoform p42 is known to be active in exponentially growing cells at several points of the cell cycle. A high basal activity was present in three cell lines representative of immature myeloid cells tested: uHL-60, AML-14, and MPD. However, DMSO-induced differentiation of HL-60 cells (dHL-60) and subsequent expression of the neutrophilic phenotype occurred with a concomitant reduction on the basal level of MAPK activity. Simultaneously, extracellular stimuli like the cytokine granulocyte/macrophage colony-stimulating factor (GM-CSF) induced a fast (<10 min) and robust response. In terms of MAPK activity, the more mature the cell was, the higher the corresponding activity, in the three differentiation series considered: AML-14 < 3D10; MPD < G-MPD; uHL-60 < dHL-60 < neutrophils. Interestingly, peripheral blood neutrophils expressed the highest (16-fold) MAPK activation level in response to GM-CSF. Finally, using the specific MAPK inhibitor PD-98059, we demonstrated that MAPK activation is needed for neutrophil chemotaxis toward interleukin-8 and its priming by GM-CSF. Since neutrophils are terminally differentiated cells, GM-CSF does not serve a purpose in proliferation, and it must trigger the recruitment of selective signal transduction pathways particular to that final stage that includes enhanced physiological functions such as chemotaxis.
Lehman
J A
JA
Department of Physiology and Biophysics, Wright State University School of Medicine, Dayton, Ohio 45435, USA.
Paul
C C
CC
Baumann
M A
MA
Gómez-Cambronero
J
J
D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019893:Ribosomal Protein S6 Kinases / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D014443:Tyrosine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019893:Ribosomal Protein S6 Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D004121:Dimethyl Sulfoxide