Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Experimental Neurology |
| Vol/bind | 156 |
| Udgave nummer | 1 |
| Sider (fra-til) | 149-64 |
| Antal sider | 15 |
| ISSN | 0014-4886 |
| DOI | |
| Status | Udgivet - 1999 |
Bibliografisk note
Copyright 1999 Academic Press.Adgang til dokumentet
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Impaired inflammatory response to glial cell death in genetically metallothionein-I- and -II-deficient mice. / Penkowa, M; Giralt, M; Moos, T; Thomsen, P S; Hernández, J; Hidalgo, J.
I: Experimental Neurology, Bind 156, Nr. 1, 1999, s. 149-64.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Impaired inflammatory response to glial cell death in genetically metallothionein-I- and -II-deficient mice
AU - Penkowa, M
AU - Giralt, M
AU - Moos, T
AU - Thomsen, P S
AU - Hernández, J
AU - Hidalgo, J
N1 - Keywords: 6-Aminonicotinamide; Animals; Astrocytes; Blood-Brain Barrier; Bone Marrow Cells; Cell Death; Coloring Agents; Granulocyte-Macrophage Colony-Stimulating Factor; Immunohistochemistry; Inflammation; Lectins; Macrophages; Metallothionein; Mice; Mice, Knockout; Microglia; Niacin; Receptors, Granulocyte Colony-Stimulating Factor; Zinc
PY - 1999
Y1 - 1999
N2 - Metallothionein I+II (MT-I+II) are acute-phase proteins which are upregulated during pathological conditions in the brain. To elucidate the neuropathological importance of MT-I+II, we have examined MT-I+II-deficient mice following ip injection with 6-aminonicotinamide (6-AN). 6-AN is antimetabolic and toxic for bone marrow cells and grey matter astrocytes. In MT+/+ mice, injection with 6-AN resulted in breakdown of the blood-brain barrier (BBB) and absence of GFAP-positive astrocytes in specific grey matter areas of the brain stem. Reactive astrocytosis encircled the damaged grey matter areas, which were heavily infiltrated by microglia/macrophages. The recruitment of hematogenous macrophages was accompanied by leakage of the BBB. The immunoreactivity (ir) of granulocyte-macrophage-colony-stimulating factor (GM-CSF) and the receptor for GM-CSF (GM-CSFrec) was significantly upregulated in astrocytes and microglia/macrophages, respectively. MT-I+IIir was also clearly increased in astrocytes surrounding the damaged areas, while that of the CNS-specific MT isoform, MT-III, was mildly increased in both astrocytes and microglia/macrophages. In MT-/- mice injected with 6-AN, the BBB remained almost intact. The damage to specific grey matter areas was similar to that observed in MT+/+ mice, but reactive astrocytosis, microglia/macrophages infiltration, and GM-CSFir and GM-CSFrecir were clearly reduced in MT-/- mice. In contrast, MT-IIIir was dramatically increased in MT-/- mice. Total zinc decreased and histochemically detectable zinc increased in the brain stem after 6-AN similarly in MT+/+ and MT-/- mice. Bone marrow myeloid monocytes and macrophages were increased as a reaction to 6-AN only in MT+/+ mice. The results demonstrate that the capability of MT-/- mice to mount a normal inflammatory response in the brain is severely attenuated, at least in part because of 6-AN-induced bone marrow affectation, involving MT-I+II for the first time as major factors during CNS tissue damage.
AB - Metallothionein I+II (MT-I+II) are acute-phase proteins which are upregulated during pathological conditions in the brain. To elucidate the neuropathological importance of MT-I+II, we have examined MT-I+II-deficient mice following ip injection with 6-aminonicotinamide (6-AN). 6-AN is antimetabolic and toxic for bone marrow cells and grey matter astrocytes. In MT+/+ mice, injection with 6-AN resulted in breakdown of the blood-brain barrier (BBB) and absence of GFAP-positive astrocytes in specific grey matter areas of the brain stem. Reactive astrocytosis encircled the damaged grey matter areas, which were heavily infiltrated by microglia/macrophages. The recruitment of hematogenous macrophages was accompanied by leakage of the BBB. The immunoreactivity (ir) of granulocyte-macrophage-colony-stimulating factor (GM-CSF) and the receptor for GM-CSF (GM-CSFrec) was significantly upregulated in astrocytes and microglia/macrophages, respectively. MT-I+IIir was also clearly increased in astrocytes surrounding the damaged areas, while that of the CNS-specific MT isoform, MT-III, was mildly increased in both astrocytes and microglia/macrophages. In MT-/- mice injected with 6-AN, the BBB remained almost intact. The damage to specific grey matter areas was similar to that observed in MT+/+ mice, but reactive astrocytosis, microglia/macrophages infiltration, and GM-CSFir and GM-CSFrecir were clearly reduced in MT-/- mice. In contrast, MT-IIIir was dramatically increased in MT-/- mice. Total zinc decreased and histochemically detectable zinc increased in the brain stem after 6-AN similarly in MT+/+ and MT-/- mice. Bone marrow myeloid monocytes and macrophages were increased as a reaction to 6-AN only in MT+/+ mice. The results demonstrate that the capability of MT-/- mice to mount a normal inflammatory response in the brain is severely attenuated, at least in part because of 6-AN-induced bone marrow affectation, involving MT-I+II for the first time as major factors during CNS tissue damage.
U2 - 10.1006/exnr.1998.7009
DO - 10.1006/exnr.1998.7009
M3 - Journal article
C2 - 10192786
VL - 156
SP - 149
EP - 164
JO - Experimental Neurology
JF - Experimental Neurology
SN - 0014-4886
IS - 1
ER -