scholarly journals Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin.

1995 ◽  
Vol 92 (13) ◽  
pp. 6132-6136 ◽  
Author(s):  
S. Kharbanda ◽  
A. Saleem ◽  
Z. Yuan ◽  
Y. Emoto ◽  
K. V. Prasad ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stimulation Of

scholarly journals Essential role for focal adhesion kinase in regulating stress hematopoiesis

Blood ◽  
2010 ◽  
Vol 116 (20) ◽  
pp. 4103-4115 ◽  
Author(s):  
Sasidhar Vemula ◽  
Baskar Ramdas ◽  
Philip Hanneman ◽  
Joseph Martin ◽  
Hilary E. Beggs ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Stress Responses ◽  
Essential Role ◽  
Bone Marrow Cells ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that has been extensively studied in fibroblasts; however its function in hematopoiesis remains an enigma. FAK is thought to be expressed in myeloid and erythroid progenitors, and its expression is enhanced in response to cytokines such as granu-locyte macrophage colony-stimulating factor. Furthermore, bone marrow cells cultured in granulocyte macrophage colony-stimulating factor show active migration and chemoattractant-induced polarization, which correlates with FAK induction. While loss of FAK in mice results in embryonic lethality, we have deleted FAK in the adult bone marrow. We show an essential role for FAK in regulating hemolytic, myelotoxic, as well as acute inflammatory stress responses in vivo. In vitro, loss of FAK in erythroid and myeloid progenitor's results in impaired cytokine induced growth and survival, as well as defects in the activation and expression of antiapoptotic proteins caspase 3 and Bcl-xL. Additionally, reduced migration and adhesion of myeloid cells on extracellular matrix proteins, as well as impaired activation of Rac GTPase is also observed in the absence of FAK. Our studies reveal an essential role for FAK in integrating growth/survival and adhesion based functions in myeloid and erythroid cells predominantly under conditions of stress.

scholarly journals Focal Adhesion Kinase Upregulated by Granulocyte-Macrophage Colony-Stimulating Factor But Not by Interleukin-3 in Differentiating Myeloid Cells

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3434-3442 ◽  
Author(s):  
Akihiro Kume ◽  
Hiroshi Nishiura ◽  
Junko Suda ◽  
Toshio Suda
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Lymphoid Cells ◽  
Colony Stimulating Factor ◽  
Murine Bone Marrow ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The involvement of focal adhesion kinase (FAK) in myeloid differentiation was investigated in primary murine bone marrow (BM) cells. In unstimulated BM, FAK mRNA was detected in myeloid and lymphoid cells, but not in erythroid precursors. When the BM cells were incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or interleukin-3 (IL-3), FAK expression showed a remarkable difference depending on the cytokine. Although FAK was upregulated in the cells stimulated by GM-CSF (GM-treated cells), the kinase was barely detectable in the cells cultured with IL-3 (IL-3–treated cells). Morphology and flow cytometry analysis showed GM-CSF promoted the growth and differentiation of monocyte/macrophage lineage stronger than IL-3. In addition, motility of the cytokine-differentiated cells showed an overt distinction between the cultures, which was closely correlated with FAK expression. After 7 days of stimulation, GM-treated cells showed active migration and chemoattractant-induced morphologic polarization. In contrast, IL-3–treated cells showed minimal migration and polarization. These results suggest an important role of GM-CSF in the terminal differentiation of monocytes/macrophages, and possible involvement of FAK in functional maturity of this lineage.

Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2645-2652 ◽  
Author(s):  
Renato Colognato ◽  
Joseph R. Slupsky ◽  
Marina Jendrach ◽  
Ladislav Burysek ◽  
Tatiana Syrovets ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Protease Activated Receptors ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Antigen Presenting ◽  
Stimulating Factor ◽  
Stimulation Of

Abstract Protease-activated receptors (PARs) are stimulated by proteolytic cleavage of their extracellular domain, unmasking a new N-terminus acting as tethered ligand. Whereas the role of PARs in platelets is well known, their presence and function in human monocytes and other antigen-presenting cells has not been characterized. Here it is demonstrated that human peripheral monocytes and monocyte-derived macrophages and dendritic cells differentially express PARs. Human monocytes express mainly PAR1 and less PAR3. Differentiation of monocytes into macrophages by either macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) elicits enhanced expression of PAR1, PAR2, and PAR3. In contrast, dendritic cells differentiated from monocytes by GM-CSF and interleukin-4 (IL-4) strongly down-regulated PAR1, PAR2, and PAR3, both at the mRNA and the protein level. Down-regulation of the PAR expression was apparently due to IL-4, because treatment of macrophages with IL-4 caused down-regulation of PAR1, PAR2, and PAR3. PAR4 mRNA expression remained undetectable in any of the cell types investigated. Stimulation of PAR1, PAR2, and PAR3 with thrombin, trypsin, or established receptor-activating peptides (PAR-APs) triggered cytosolic Ca2+ responses, indicating functionally active PARs. Further, stimulation of monocytes or macrophages with thrombin or PAR1-AP, but not with PAR2-or PAR4-AP, triggers expression of monocyte chemoattractant protein-1 (MCP-1) both at the mRNA and the protein level. These data demonstrate that differentiation of human monocytes is associated with differential expression of functionally active PARs that mediate distinct regulatory functions in inflammation and atherogenesis. (Blood. 2003;102:2645-2652)

scholarly journals Expression of the macrophage-specific colony-stimulating factor in human monocytes treated with granulocyte-macrophage colony-stimulating factor

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1259-1261
Author(s):  
J Horiguchi ◽  
MK Warren ◽  
D Kufe
Keyword(s):  
T Cells ◽  
Gene Product ◽  
Phorbol Ester ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Activated Monocytes ◽  
Macrophage Colony ◽  
Stimulating Factor

The macrophage-specific colony-stimulating factor (CSF-1, M-CSF) regulates the survival, growth and differentiation of monocytes. We have recently demonstrated that phorbol ester induces expression of CSF- 1 in human monocytes. These findings suggested that activated monocytes are capable of producing their own lineage-specific CSF. The present studies demonstrate that the granulocyte-macrophage colony-stimulating factor (GM-CSF) also induces CSF-1 transcripts in monocytes. Furthermore, we demonstrate that the detection of CSF-1 RNA in GM-CSF- treated monocytes is associated with synthesis of the CSF-1 gene product. The results thus suggest that GM-CSF may indirectly control specific monocyte functions through the regulation of CSF-1 production. These findings indicate another level of interaction between T cells and monocytes.

scholarly journals Coinduction of granulocyte-macrophage colony-stimulating factor release and lymphokine-activated killer cell susceptibility in monocytes by interleukin-2 via interleukin-2 receptor beta

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3130-3137 ◽  
Author(s):  
PK Epling-Burnette ◽  
S Wei ◽  
DK Blanchard ◽  
E Spranzi ◽  
JY Djeu
Keyword(s):  
Interleukin 2 ◽  
Lak Cells ◽  
Human Monocytes ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Interleukin 2 Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Receptor Beta

Abstract Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. By a 5-hour 51Cr-release assay, monocytes cultured in IL-2 were found to gain increasing susceptibility to LAK cells with time and this effect was dose dependent. Maximal susceptibility was obtained with a 4-day culture in 1,000 U/mL of IL-2. Monocytes were also found to release GM-CSF in response to IL-2 using a CSF-dependent cell line, Mo7e. Because IL-2- induced GM-CSF release coincides with LAK lysis of IL-2-cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM- CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells.

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