PMID- 15363038 OWN - NLM STAT- MEDLINE DCOM- 20050203 LR - 20181130 IS - 1320-5463 (Print) IS - 1320-5463 (Linking) VI - 54 IP - 9 DP - 2004 Sep TI - GM-CSF activates RhoA, integrin and MMP expression in human monocytic cells. PG - 693-702 AB - Monocyte migration is one of the key events occurring in the early stage of atherosclerosis. This process includes monocytic adhesion to and penetration through the arterial intima. In such an environment, many factors stimulate the monocytes to enhance integrin activation and extracellular matrix degradation. To investigate the coordinative operation of these two events in relation to monocyte migration, we paid particular attention to the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on monocytes in terms of RhoA activation and matrix metalloproteinase (MMP) expression. RhoA and integrin clustering were activated by GM-CSF, monocyte chemoattractant protein-1 (MCP-1) and platelet-derived growth factor-BB (PDGF-BB) in human monocytic cell lines. Furthermore, enhancement of migration was observed with stimulation by MCP-1 and PDGF-BB. Granulocyte-macrophage colony-stimulating factor did not enhance the migration, even though it activated RhoA and integrin. However, GM-CSF is known to stimulate monocytes to express MCP-1, suggesting the presence of an indirect mechanism for GM-CSF-mediated migratory activity. In contrast, only GM-CSF enhanced the expression of MMP-1 and MMP-9. These results provide evidence that GM-CSF has multiple functions enhancing monocytic migration via RhoA and integrin activation, and via MMP expression. FAU - Kohno, Yukari AU - Kohno Y AD - Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. FAU - Tanimoto, Akihide AU - Tanimoto A FAU - Cirathaworn, Cintana AU - Cirathaworn C FAU - Shimajiri, Shohei AU - Shimajiri S FAU - Tawara, Akihiko AU - Tawara A FAU - Sasaguri, Yasuyuki AU - Sasaguri Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Australia TA - Pathol Int JT - Pathology international JID - 9431380 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Integrins) RN - 0 (Platelet-Derived Growth Factor) RN - 0 (Proto-Oncogene Proteins c-sis) RN - 0 (RNA, Messenger) RN - 124671-05-2 (RHOA protein, human) RN - 1B56C968OA (Becaplermin) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - EC 1.13.12.- (Luciferases) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Becaplermin MH - Blotting, Northern MH - Cell Line MH - Cell Movement/drug effects MH - Chemokine CCL2/pharmacology MH - Genes, Reporter MH - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology/physiology MH - Humans MH - Integrins/*biosynthesis MH - Luciferases MH - Matrix Metalloproteinases/*biosynthesis/genetics MH - Monocytes/*drug effects/metabolism MH - Platelet-Derived Growth Factor/pharmacology MH - Proto-Oncogene Proteins c-sis MH - RNA, Messenger/metabolism MH - rhoA GTP-Binding Protein/*biosynthesis EDAT- 2004/09/15 05:00 MHDA- 2005/02/04 09:00 CRDT- 2004/09/15 05:00 PHST- 2004/09/15 05:00 [pubmed] PHST- 2005/02/04 09:00 [medline] PHST- 2004/09/15 05:00 [entrez] AID - PIN1682 [pii] AID - 10.1111/j.1440-1827.2004.01682.x [doi] PST - ppublish SO - Pathol Int. 2004 Sep;54(9):693-702. doi: 10.1111/j.1440-1827.2004.01682.x.