Generation, characterization and biological activity of CCL2 (MCP-1/JE) and CCL12 (MCP-5) specific antibodies.
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.
Tsui
Ping
P
Department of Molecular Discovery Technologies, Discovery Research, Centocor R&D Inc., 145 King of Prussia Road, Radnor, PA 19087, USA.
Das
Anuk
A
Whitaker
Brian
B
Tornetta
Mark
M
Stowell
Nicole
N
Kesavan
Prabakaran
P
Kaiser
Elisabeth
E
Lacy
Eilyn R
ER
Yan
Li
L
Snyder
Linda A
LA
Sweet
Raymond
R
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D009500:Neutralization Tests
D000906:Antibodies; C491224:Ccl12 protein, mouse; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018945:Monocyte Chemoattractant Proteins; D002118:Calcium