MCP-1-stimulated chemotaxis of monocytic and endothelial cells is dependent on activation of different signaling cascades.
Monocyte chemoattractant protein-1 (MCP-1) is important in attracting monocytes to sites of inflammation. Besides induction of monocyte recruitment, MCP-1 can also affect chemotactic response of endothelial cells. The molecular mechanisms involved in MCP-1-induced cell migration are poorly understood. In the current investigation, we demonstrate activation of p42/44(ERK1/2) and p38 mitogen-activated protein kinases (MAPKs), phosphatydilinositol-3-kinase (PI3K) and Src-kinases in both monocytes and endothelial cells stimulated with MCP-1 in vitro. The response was rapid and time-dependent, detectable within 3 min of MCP-1 stimulation. MCP-1-induced phosphorylation of p42/44(ERK1/2) MAPKs was partially blocked by inhibitor of PI3K LY294002, while phosphorylation of p38 MAPK was diminished to a greater extent in presence of Src-kinase inhibitor PP2. There was a substantial inhibition of monocyte migration upon treatment with inhibitors of p38 MAPK, at the same time inhibition of p42/44(ERK1/2) MAPK activation had no effect. On the contrary, the MCP-1-stimulated chemotaxis of endothelial cells was completely abolished by inhibitors of PI3K and p42/44(ERK1/2), but not by p38 MAPK inhibitors. These results suggest that parallel signal transduction pathways are activated by MCP-1, and that depending on the cell type these pathways differentially contribute to cell chemotactic activity.
Arefieva
Tatiana I
TI
Institute of Experimental Cardiology, Cardiology Research Centre, Moscow, Russian Federation.
Kukhtina
Nadezhda B
NB
Antonova
Olga A
OA
Krasnikova
Tatiana L
TL
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects* / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000502:physiology
D018932:Chemokine CCL2; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases