Signal transduction pathways involved in soluble fractalkine-induced monocytic cell adhesion.
Fractalkine displays features that distinguishes it from the other chemokines. In particular, besides its chemoattractant action it promotes, under physiologic flow, the rapid capture and the firm adhesion of a subset of leukocytes or intervenes in the neuron/microglia interaction. This study verified that indeed the human monocytic MonoMac6 cell line adheres to fibronectin-coated filters in response to soluble fractalkine (s-FKN). s-FKN stimulates, with distinct time courses, extracellular signal-related kinases (ERK1 and ERK2) and stress-activated protein kinases (SAPK1/JNK1 and SAPK2/p38). Both p60 Src and p72 Syk were activated under s-FKN stimulation with a rapid kinetic profile compatible with a downstream regulation on the mitogen-activated protein kinase (MAPK) congeners. The use of specific tyrosine kinase inhibitors revealed that the ERK pathway is strictly controlled by Syk, whereas c-Src up-regulated the downstream SAPK2/p38. In contrast, the SAPK1/JNK1 pathway was not regulated by any of these nonreceptor tyrosine kinases. The s-FKN-mediated increased adherence of MonoMac6 cells was partially inhibited by SB202190, a broad SAPKs inhibitor, PD98059, an MEK inhibitor, LY294002, a phosphatidyl inositol 3-kinase inhibitor, and a pertussis toxin-sensitive G protein. These data highlight that the integration of a complex array of signal transduction pathways is necessary to complete the full s-FNK-dependent adherence of human monocytic cells to fibronectin. (Blood. 2001;97:2031-2037)
INSERM U364, Facultè de Mèdecine, Nice Cedex 02, France.
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B
Cambien
M
M
Pomeranz
H
H
Schmid-Antomarchi
M A
MA
Millet
V
V
Breittmayer
B
B
Rossi
A
A
Schmid-Alliana
D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D018121:Receptors, Cytokine / Q000187:drug effects / Q000502:physiology*; D015728:Receptors, HIV / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000072377:Syk Kinase; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D019743:Chemokines, CXC; D002772:Cholera Toxin; D002867:Chromones; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D005353:Fibronectins; D005419:Flavonoids; D019204:GTP-Binding Proteins; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D011725:Pyridines; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D000072377:Syk Kinase; D010566:Virulence Factors, Bordetella; D048051:p38 Mitogen-Activated Protein Kinases; C515538:CX3CL1 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C000606896:SYK protein, human; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one