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Generation, characterization and biological activity of CCL2 (MCP-1/JE) and CCL12 (MCP-5) specific antibodies

Generation, characterization and biological activity of CCL2 (MCP-1/JE) and CCL12 (MCP-5)... The human CCL2 chemokine is implicated in many chronic inflammatory conditions. In the mouse, there are two CCL2 homologues, CCL2 (MCP-1/JE) and CCL12 (MCP-5). Both are potent monocyte chemoattractants and bind to and activate the same receptor, CCR2. The overlapping activities of these chemokines complicate the design of mouse model studies that are intended to mimic human disease. To study the roles of CCL2 and CCL12, we generated neutralizing antibodies specific to each chemokine. Consistent with binding and affinity analyses, the antibodies specifically inhibited CCL2- or CCL12- mediated Ca ^{2+} mobilization in THP-1 cells. When tested in nude mice bearing human PANC-1 pancreatic tumor cells in Matrigel™ plugs, CCL2 and CCL12 antibodies potently inhibited tumor angiogenesis, indicating that both CCL2 and CCL12 may contribute to tumor angiogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Human Antibodies IOS Press

Generation, characterization and biological activity of CCL2 (MCP-1/JE) and CCL12 (MCP-5) specific antibodies

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Publisher
IOS Press
Copyright
Copyright © 2007 by IOS Press, Inc
ISSN
1093-2607
eISSN
1875-869X
Publisher site
See Article on Publisher Site

Abstract

The human CCL2 chemokine is implicated in many chronic inflammatory conditions. In the mouse, there are two CCL2 homologues, CCL2 (MCP-1/JE) and CCL12 (MCP-5). Both are potent monocyte chemoattractants and bind to and activate the same receptor, CCR2. The overlapping activities of these chemokines complicate the design of mouse model studies that are intended to mimic human disease. To study the roles of CCL2 and CCL12, we generated neutralizing antibodies specific to each chemokine. Consistent with binding and affinity analyses, the antibodies specifically inhibited CCL2- or CCL12- mediated Ca ^{2+} mobilization in THP-1 cells. When tested in nude mice bearing human PANC-1 pancreatic tumor cells in Matrigel™ plugs, CCL2 and CCL12 antibodies potently inhibited tumor angiogenesis, indicating that both CCL2 and CCL12 may contribute to tumor angiogenesis.

Journal

Human AntibodiesIOS Press

Published: Jan 1, 2007

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