In vivo MR evaluation of the effect of the CCR2 antagonist on macrophage migration.
The CCR2 antagonist is a receptor antagonist for monocyte chemoattractant protein-1 and is known to be a potential anti-inflammatory therapeutic agent. Recently used optimized labeling techniques for superparamagnetic iron oxide, macrophage homing, and recruitment toward the infection site can be observed on in vivo MRI. This study details the effect of the CCR2 antagonist on the macrophage migration and the feasibility of in vivo MRI for assessing the inhibition of chemotactic activity by the CCR2 antagonist. On binding assay, the CCR2 antagonist inhibits the binding affinity of monocyte chemoattractant protein-1 to CCR2. Increased expression of messenger ribonucleic acid (mRNA) and expression of CCR2 and CD11b on the cellular surface, as induced by monocyte chemoattractant protein-1, was shown, and the effect of monocyte chemoattractant protein-1 on CCR2 and CD11b was restricted by the CCR2 antagonist. In a migration test using the transwell system, macrophages treated with the CCR2 antagonist showed significantly decreased chemotactic migration compared to that of wild-type macrophages. MR images of infected left calf muscles in 12 mice were obtained 24 h after administration of macrophages labeled with superparamagnetic iron oxide. MRI successfully demonstrated the effect of the CCR2 antagonist on the directional migration of macrophages.
Lee
Yedaun
Y
Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
Ryu
Je-Won
JW
Chang
Hyeujin
H
Sohn
Jin Young
JY
Lee
Kyung Won
KW
Woo
Chul Woong
CW
Kang
Hee Jung
HJ
Jeong
Seong-Yun
SY
Choi
Eun Kyung
EK
Lee
Jin Seong
JS
D000818:Animals; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation; D008264:Macrophages / Q000000981:diagnostic imaging / Q000187:drug effects*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013141:Spiro Compounds / Q000494:pharmacology
D039481:CD11b Antigen; D018932:Chemokine CCL2; D010880:Piperidines; D012333:RNA, Messenger; D054390:Receptors, CCR2; D013141:Spiro Compounds