PMID- 19745197 OWN - NLM STAT- MEDLINE DCOM- 20091203 LR - 20141120 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 29 IP - 12 DP - 2009 Dec TI - Tumor necrosis factor-alpha potentiates RhoA-mediated monocyte transmigratory activity in vivo at a picomolar level. PG - 2138-45 LID - 10.1161/ATVBAHA.109.195735 [doi] AB - OBJECTIVE: The serum level of tumor necrosis factor-alpha (TNF-alpha) is in the picomolar range under inflammatory conditions. We investigated whether these picomolar levels of TNF-alpha directly modulate the functional activities of circulating monocytes. METHODS AND RESULTS: In THP-1 monocytes treated with TNF-alpha (1 to 100 pmol/L/30 minutes), cytosolic RhoA small GTPase rapidly translocated to the plasma membrane via functionally active ezrin/radixin/moesin (ERM) complex, a cytoskeletal linker, and subsequent actin polymerization through NF-kappaB activation. The threonine phosphorylation of ERM was accomplished by the activation of TNF receptor type I (TNFRI) and signaling pathways involving PI3K and an atypical PKC; ie, PKCzeta. The TNF-alpha-treated monocytes (10 pmol/L) displayed more potent and prolonged generation of GTP-bound RhoA in response to secondary stimulation with RhoA-activating monocyte chemoattractant protein-1 (MCP-1). Clearly, human circulating monocytes preconditioned by 10 pmol/L TNF-alpha augmented MCP-1-mediated chemotaxis and firm adhesion on VCAM-1 and ICAM-1 in vitro and ex vivo. The elevation of serum TNF-alpha (>5 pmol/L within 16 hours), which was introduced by intraperitoneal injection of mouse-specific TNF-alpha to C57/BL6 mice, enhanced the number of CD80+ monocytes transmigrating to the JE/MCP-1-injected intraperitoneal space. CONCLUSIONS: Picomolar concentrations of TNF-alpha in the bloodstream may prime the RhoA-dependent activities of circulating monocytes to enhance recruitment to active inflammatory foci. FAU - Lim, Sunny AU - Lim S AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. FAU - Ryu, Jewon AU - Ryu J FAU - Shin, Jin-Ae AU - Shin JA FAU - Shin, Min-Jung AU - Shin MJ FAU - Ahn, Yeong Ki AU - Ahn YK FAU - Kim, Jae Joong AU - Kim JJ FAU - Han, Ki Hoon AU - Han KH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090910 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Cytoskeletal Proteins) RN - 0 (Membrane Proteins) RN - 0 (Microfilament Proteins) RN - 0 (NF-kappa B) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (ezrin) RN - 124671-05-2 (RHOA protein, human) RN - 144131-77-1 (moesin) RN - 144517-21-5 (radixin) RN - EC 3.6.5.2 (RhoA protein, mouse) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Animals MH - Biological Transport, Active/drug effects MH - Cell Line MH - Cell Membrane/drug effects/metabolism MH - Cell Movement/drug effects/physiology MH - Chemokine CCL2/pharmacology MH - Cytoskeletal Proteins/metabolism MH - Humans MH - In Vitro Techniques MH - Macrophages, Peritoneal/drug effects/physiology MH - Male MH - Membrane Proteins/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microfilament Proteins/metabolism MH - Monocytes/*drug effects/*physiology MH - NF-kappa B/metabolism MH - Peritoneal Cavity/cytology MH - Phosphorylation MH - Receptors, Tumor Necrosis Factor, Type I/metabolism MH - Recombinant Proteins/pharmacology MH - Tumor Necrosis Factor-alpha/administration & dosage/*pharmacology MH - rho GTP-Binding Proteins/*physiology MH - rhoA GTP-Binding Protein/*physiology EDAT- 2009/09/12 06:00 MHDA- 2009/12/16 06:00 CRDT- 2009/09/12 06:00 PHST- 2009/09/12 06:00 [entrez] PHST- 2009/09/12 06:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - ATVBAHA.109.195735 [pii] AID - 10.1161/ATVBAHA.109.195735 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):2138-45. doi: 10.1161/ATVBAHA.109.195735. Epub 2009 Sep 10.