PMID- 25452166
OWN - NLM
STAT- MEDLINE
DCOM- 20151029
LR  - 20181113
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 63
IP  - 4
DP  - 2015 Apr
TI  - Macrophages in spinal cord injury: phenotypic and functional change from exposure 
      to myelin debris.
PG  - 635-51
LID - 10.1002/glia.22774 [doi]
AB  - Macrophage activation and persistent inflammation contribute to the pathological 
      process of spinal cord injury (SCI). It was reported that M2 macrophages were 
      induced at 3-7 days after SCI but M2 markers were reduced or eliminated after 1 
      week. By contrast, M1 macrophage response is rapidly induced and then maintained 
      at injured spinal cord. However, factors that modulate macrophage phenotype and 
      function are poorly understood. We developed a model to distinguish bone-marrow 
      derived macrophages (BMDMs) from residential microglia and explored how BMDMs 
      change their phenotype and functions in response to the lesion-related factors in 
      injured spinal cord. Infiltrating BMDMs expressing higher Mac-2 and lower CX3CR1 
      migrate to the epicenter of injury, while microglia expressing lower Mac-2 but 
      higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site 
      switches BMDMs from M2 phenotype towards M1-like phenotype. Myelin debris 
      activates ATP-binding cassette transporter A1 (ABCA1) for cholesterol efflux in 
      response to myelin debris loading in vitro. However, this homeostatic mechanism 
      in injured site is overwhelmed, leading to the development of foamy macrophages 
      and lipid plaque in the lesion site. The persistence of these cells indicates a 
      pro-inflammatory environment, associated with enhanced neurotoxicity and impaired 
      wound healing. These foamy macrophages have poor capacity to phagocytose 
      apoptotic neutrophils resulting in uningested neutrophils releasing their toxic 
      contents and further tissue damage. In conclusion, these data demonstrate for the 
      first time that myelin debris generated in injured spinal cord modulates 
      macrophage activation. Lipid accumulation following macrophage phenotype switch 
      contributes to SCI pathology.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Wang, Xi
AU  - Wang X
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, The State University 
      of New Jersey, New Jersey; Institute of Neurosciences, the Fourth Military 
      Medical University, Xian, China.
FAU - Cao, Kai
AU  - Cao K
FAU - Sun, Xin
AU  - Sun X
FAU - Chen, Yongxiong
AU  - Chen Y
FAU - Duan, Zhaoxia
AU  - Duan Z
FAU - Sun, Li
AU  - Sun L
FAU - Guo, Lei
AU  - Guo L
FAU - Bai, Paul
AU  - Bai P
FAU - Sun, Dongming
AU  - Sun D
FAU - Fan, Jianqing
AU  - Fan J
FAU - He, Xijing
AU  - He X
FAU - Young, Wise
AU  - Young W
FAU - Ren, Yi
AU  - Ren Y
LA  - eng
GR  - R01 GM100474/GM/NIGMS NIH HHS/United States
GR  - R01GM100474-03/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20141128
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (ABCA1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (Biomarkers)
RN  - 0 (CX3C Chemokine Receptor 1)
RN  - 0 (Cx3cr1 protein, mouse)
RN  - 0 (Galectin 3)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Receptors, Chemokine)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/metabolism
MH  - Animals
MH  - Biomarkers/metabolism
MH  - CX3C Chemokine Receptor 1
MH  - Disease Models, Animal
MH  - Galectin 3/metabolism
MH  - Inflammation/metabolism
MH  - Macrophage Activation/*immunology
MH  - Macrophage-1 Antigen/metabolism
MH  - Macrophages/cytology/immunology/*metabolism
MH  - Mice
MH  - Microglia/cytology/*immunology
MH  - Myelin Sheath/immunology/*metabolism
MH  - Phagocytosis/immunology
MH  - Receptors, Chemokine/metabolism
MH  - Signal Transduction/*immunology
MH  - Spinal Cord Injuries/*immunology/metabolism
PMC - PMC4331228
MID - NIHMS643077
OTO - NOTNLM
OT  - foamy cells
OT  - macrophages
OT  - myelin debris
OT  - spinal cord injury
COIS- Conflict of Interest The authors declare no competing financial interests.
EDAT- 2014/12/03 06:00
MHDA- 2015/10/30 06:00
PMCR- 2016/04/01
CRDT- 2014/12/03 06:00
PHST- 2014/04/11 00:00 [received]
PHST- 2014/11/05 00:00 [revised]
PHST- 2014/11/12 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/10/30 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1002/glia.22774 [doi]
PST - ppublish
SO  - Glia. 2015 Apr;63(4):635-51. doi: 10.1002/glia.22774. Epub 2014 Nov 28.