ProBDNF inhibits infiltration of ED1+ macrophages after spinal cord injury.
The central nervous system (CNS) does not regenerate partly due to the slow clearance of debris from the degenerated myelin sheath by Wallerian degeneration. The mechanism underlying the inefficiency in myelin clearance is not clear. Here we showed that endogenous proBDNF may inhibit the infiltration of ED1+ inflammatory cells after spinal cord injury. After injury, proBDNF and its receptors sortilin and p75NTR are expressed in the spinal cord as determined by Western blots and immunocytochemistry. ProBDNF and mature BDNF were released from macrophages in vitro. Macrophages in vivo (ED1+) and isolated in vitro (CD11b+) express moderate levels of proBDNF, sortilin and p75NTR. ProBDNF suppressed the migration of isolated macrophages in vitro and the antibody to proBDNF enhanced the migration. Suppression of proBDNF in vivo by administering the antiserum to the prodomain of BDNF after spinal cord injury (SCI) increased the infiltration of macrophages and increased number of neurons in the injured cord. BBB tests showed that the treatment of the antibody to proBDNF improved the functional recovery after spinal cord injury. Our data suggest that proBDNF is a suppressing factor for macrophage migration and infiltration and may play a detrimental role after SCI.
Wong
Ira
I
Department of Human Physiology and Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia.
Liao
Hong
H
Bai
Xianshu
X
Zaknic
Antony
A
Zhong
Jinhua
J
Guan
Yue
Y
Li
Hong-Yun
HY
Wang
Yan-Jiang
YJ
Zhou
Xin-Fu
XF
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism*; D039481:CD11b Antigen; D002464:Cell Migration Inhibition / Q000276:immunology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053331:Ectodysplasins; D005260:Female; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D009419:Nerve Tissue Proteins; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D020127:Recovery of Function; D013116:Spinal Cord / Q000166:cytology; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000378:metabolism; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D019208:Brain-Derived Neurotrophic Factor; D039481:CD11b Antigen; D053331:Ectodysplasins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D000099183:Sortilin; C426674:brain-derived neurotrophic factor precursor; C068313:Ngfr protein, rat