Nonrequirement of continuous stimulation with MCP-1 for cell migration and determination of directional migration by initial stimulation with chemokine.
Monocyte chemoattractant protein-1 (MCP-1) induces monocyte migration through interaction with the MCP-1 receptor CCR2. In this report we have examined the length of chemokine stimulation necessary for induction of cell migration and whether continuous stimulation is required for active migration. Monocytic THP-1 cells prestimulated with MCP-1 for 15 to 30 min exhibited a migration response after the chemokine was removed from the culture medium, indicating that a short exposure to chemokine stimulation is sufficient for migration of THP-1 cells and continuous stimulation is not required for active migration. A reverse gradient of MCP-1 had no effect on migration after prestimulation with MCP-1. This implies that cells are determined to directionally migrate by initial stimulation with MCP-1. Furthermore, cell migration after prestimulation with MCP-1 was inhibited by a p38 inhibitor, but not by a phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, indicating that p38, but not PI3-kinase, is involved in the migration response after the determination of direction by initial chemokine stimulation.
Kito
Keiji
K
New Product Research Laboratories II, Daiichi Pharmaceutical Company Ltd. Tokyo, Japan.
Nishida
Ken ichi
Ki
D000730:Androstadienes / Q000494:pharmacology; D002450:Cell Communication; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases
D000730:Androstadienes; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D007093:Imidazoles; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D000077191:Wortmannin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580