Monocyte recruitment and myelin removal are delayed following spinal cord injury in mice with CCR2 chemokine receptor deletion.
The inflammatory response initiated after spinal cord injury (SCI) is characterized by the accumulation of macrophages at the impact site. Monocyte chemoattractant protein-1 (MCP-1) is a strong candidate for mediating chemotaxis of monocytes to the injured nervous system. To help in defining the role of MCP-1 in inflammation after SCI, we evaluated the time course of macrophage accumulation for 2 weeks following a midthoracic spinal cord contusion injury in mice lacking CCR2, a principal receptor for MCP-1. Mice with a deletion of CCR2 resulted in significantly reduced Mac-1 immunoreactivity restricted to the lesion epicenter at 7 days postinjury. The regions devoid of Mac-1 immunoreactivity corresponded to areas of reduced myelin degradation at this time. By 14 days postinjury, however, there were no differences in Mac-1 staining between CCR2 (+/+) and CCR2 (-/-) mice. Analyses of mRNA levels by RNase protection assay (RPA) revealed increases in MCP-1 as well as MCP-3 and MIP-2 mRNA at 1 day postinjury compared with 7 day postinjury. There were no differences in chemokine expression between CCR2-deficient mice and wild-type littermate controls. The CCR2-deficient mice also exhibited reduced expression of mRNA for chemokine receptors CCR1 and CCR5. Together, these results indicate that chemokines acting through CCR2 contribute to the early recruitment of monocytes to the lesion epicenter following SCI.
Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio, USA.
Manhong
M
Ma
Tao
T
Wei
Landin
L
Boring
Israel F
IF
Charo
Richard M
RM
Ransohoff
Lyn B
LB
Jakeman
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003288:Contusions; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D013997:Time Factors
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine