MAP kinase upregulation after hematopoietic differentiation: role of chemotaxis

• Published in: American Journal of Physiology: Cell Physiology Vol. 280; no. 1; pp. C183 - C191
• Main Authors: Lehman, Jason A, Paul, Cassandra C, Baumann, Michael A, Gomez-Cambronero, Julian
• Format: Journal Article
• Language: English
• Published: United States 01.01.2001
• Subjects: Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell Line - cytology; Cell Line - drug effects; Cell Line - metabolism; Chemotaxis - drug effects; Chemotaxis - physiology; Dimethyl Sulfoxide - pharmacology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Hematopoiesis - drug effects; Hematopoiesis - physiology; HL-60 Cells - cytology; HL-60 Cells - drug effects; HL-60 Cells - metabolism; Humans; Mitogen-Activated Protein Kinase 1 - drug effects; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinases - drug effects; Mitogen-Activated Protein Kinases - metabolism; Myeloid Progenitor Cells - cytology; Myeloid Progenitor Cells - drug effects; Myeloid Progenitor Cells - metabolism; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - metabolism; Phosphorylation - drug effects; Ribosomal Protein S6 Kinases - drug effects; Ribosomal Protein S6 Kinases - metabolism; Tyrosine - metabolism; Up-Regulation - drug effects; Up-Regulation - physiology
• DOI: 10.1152/ajpcell.2001.280.1.c183
• ISSN: 0363-6143

Departments of 1  Physiology and Biophysics and 2  Medicine, Wright State University School of Medicine, Dayton 45435; and 3  Research Service, Dayton Veterans Affairs Medical Center, Dayton, Ohio 45428 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. mitogen-activated protein kinase; granulocyte/macrophage colony-stimulating factor; neutrophils; cell differentiation; leukemic cells