PMID- 8926037
OWN - NLM
STAT- MEDLINE
DCOM- 19961029
LR  - 20220228
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 15
IP  - 4
DP  - 1995 Dec
TI  - The role of macrophages, perivascular cells, and microglial cells in the 
      pathogenesis of experimental autoimmune encephalomyelitis.
PG  - 437-46
AB  - Clinical signs of experimental autoimmune encephalomyelitis (EAE) in rats can be 
      suppressed by treatment with liposomes containing dichloromethylene diphosphonate 
      (Cl2MDP liposomes). Here we investigated whether besides the blood-borne 
      macrophages also ED2+ perivascular cells and microglia are affected by this 
      treatment. For this purpose we examined the central nervous system of bone marrow 
      chimeras in which EAE was induced with encephalitogenic T cells. Quantification 
      of cell numbers of various cell types in inflammatory lesions in the spinal cord 
      showed that after treatment with Cl2MDP liposomes more than 95% of the bone 
      marrow derived (I1-69+) macrophages were eliminated. In addition the number of 
      ED2+ perivascular cells were seen to be decreased by 68% as compared to ED2+ 
      cells in control liposome treated animals. However the number of these 
      perivascular cells in Cl2MDP liposome treated animals did not differ from the 
      number of perivascular cells in naive animals, indicating that only newly 
      recruited, inflammation associated, ED2+ macrophages were eliminated. Moreover, 
      detection of degenerating nuclei by in situ nick translation (ISNT) in 
      combination with staining for ED1 or ED2 showed that in the perivascular space no 
      degenerating cells were present. Cl2MDP liposome treatment furthermore decreased 
      the numbers of T cells infiltrating the parenchyma by more than 50%. Instead T 
      cells were found in large numbers in the perivascular space. Microglia did not 
      seem to be eliminated by Cl2MDP liposome treatment as shown by the absence of 
      ED1+/ISNT+ cells in the CNS parenchyma. However the number of ED1+ (I1-69-) 
      microglial cells decreased by more than 80%, indicating that the activation of 
      this cell type was impaired. It is concluded that bone marrow derived macrophages 
      play an important role in the pathogenesis of EAE via interactions with 
      lymphocytes and the activation of resident microglia.
FAU - Bauer, J
AU  - Bauer J
AD  - Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, 
      Netherlands.
FAU - Huitinga, I
AU  - Huitinga I
FAU - Zhao, W
AU  - Zhao W
FAU - Lassmann, H
AU  - Lassmann H
FAU - Hickey, W F
AU  - Hickey WF
FAU - Dijkstra, C D
AU  - Dijkstra CD
LA  - eng
GR  - NS-27321/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
SB  - IM
MH  - Animals
MH  - Central Nervous System/*blood supply/pathology
MH  - Encephalomyelitis, Autoimmune, Experimental/*etiology/*immunology
MH  - Macrophages/*immunology/pathology
MH  - Microglia/*immunology/pathology
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Inbred Lew
MH  - Spinal Cord/pathology
MH  - Spleen/pathology
MH  - T-Lymphocytes/immunology/metabolism/pathology
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - 10.1002/glia.440150407 [doi]
PST - ppublish
SO  - Glia. 1995 Dec;15(4):437-46. doi: 10.1002/glia.440150407.