| 1. |
- Hietala, Max Albert, 1969, et al.
(författare)
-
Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis.
- 2004
-
Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 34:4, s. 1208-16
-
Tidskriftsartikel (refereegranskat)abstract
- To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3- and factor B (FB)-deficient (C3(-/-) and FB(-/-)) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3(-/-) mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB(-/-) mice ranked intermediate in comparison with C3(-/-) and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3(-/-) and FB(-/-) mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.
|
|
| 2. |
- Larsson, Åsa, et al.
(författare)
-
Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(-/-)Vim(-/-) mice
- 2004
-
Ingår i: Neurochem Res. - : Springer Science and Business Media LLC. - 0364-3190. ; 29:11, s. 2069-73
-
Tidskriftsartikel (refereegranskat)abstract
- In response to central nervous system (CNS) injury, and more discretely so also during aging, astrocytes become reactive and increase their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Studies of mice deficient in astrocytic intermediate filaments have provided insights into the function of reactive gliosis. Recently we demonstrated robust integration of retinal transplants (1) and increased posttraumatic synaptic regeneration (2) in GFAP(-/-)Vim(-/-) mice, suggesting that modulation of astrocyte activity affects the permissiveness of the CNS environment for regeneration. Neurogenesis in the adult mammalian CNS is restricted to essentially two regions, the hippocampus and the subventricular zone. Here, we assessed neurogenesis in the hippocampus of 18-month-old GFAP(-/-)Vim(-/-) mice. In the granular layer of the dentate gyrus, cell proliferation/survival was 34% higher and neurogenesis 36% higher in GFAP(-/-)Vim(-/-) mice than in wildtype controls. These findings suggest that the adult hippocampal neurogenesis in healthy old mice can be increased by modulating astrocyte reactivity.
|
|
| 3. |
- Pekny, Milos, 1965, et al.
(författare)
-
Astrocyte intermediate filaments in CNS pathologies and regeneration.
- 2004
-
Ingår i: The Journal of pathology. - : Wiley. - 0022-3417. ; 204:4, s. 428-37
-
Forskningsöversikt (refereegranskat)abstract
- Astroglial cells are the most abundant cells in the mammalian central nervous system (CNS), yet our knowledge about their function in health and disease has been limited. This review focuses on the recent work addressing the function of intermediate filaments in astroglial cells under severe mechanical or osmotic stress, in hypoxia, and in brain and spinal cord injury. Recent data show that when astrocyte intermediate filaments are genetically ablated in mice, reactive gliosis is attenuated and the course of several CNS pathologies is altered, while the signs of CNS regeneration become more prominent. GFAP is the principal astrocyte intermediate filament protein and dominant mutations in the GFAP gene have been shown to lead to Alexander disease, a fatal neurodegenerative condition in humans.
|
|
| 4. |
|
|
| 5. |
- Persson, Linda, 1971, et al.
(författare)
-
Lack of complement factor C3, but not factor B, increases hyperlipidemia and atherosclerosis in apolipoprotein E-/- low-density lipoprotein receptor-/- mice
- 2004
-
Ingår i: Arterioscler Thromb Vasc Biol. - 1079-5642. ; 24:6, s. 1062-1067
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the effect of complement deficiency on atherogenesis and lipidemia, we used mice deficient in the third complement component (C3-/-) or factor B (FB-/-). METHODS AND RESULTS: Complement-deficient mice were crossed with mice deficient in both apolipoprotein E and the low-density lipoprotein receptor (Apoe-/- LDLR-/-). The percent lesion area in the aorta at 16 weeks, determined by en face analysis, was 84% higher in C3-/- mice than in controls (11.8%+/-0.4% versus 6.4%+/-0.8%, mean+/-SEM, P<0.00005). The C3-/- mice also had 58% higher serum triglyceride levels (P<0.05) and a more proatherogenic lipoprotein profile, with significantly more low-density lipoprotein cholesterol and very-low-density lipoprotein triglycerides than control mice. The C3-/- mice weighed 13% less (P<0.01) and had a lower body fat content (3.5%+/-1.0% versus 13.1%+/-3.0%, P<0.01). There were no differences between FB-/- mice and controls. CONCLUSIONS: Complement activation by the classical or lectin pathway exerts atheroprotective effects, possibly through the regulation of lipid metabolism.
|
|
| 6. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
-
Absence of glial fibrillary acidic protein and vimentin prevents hypertrophy of astrocytic processes and improves post-traumatic regeneration
- 2004
-
Ingår i: J Neurosci. - 1529-2401. ; 24:21, s. 5016-21
-
Tidskriftsartikel (refereegranskat)abstract
- The regenerative capacity of the CNS is extremely limited. The reason for this is unclear, but glial cell involvement has been suspected, and oligodendrocytes have been implicated as inhibitors of neuroregeneration (Chen et al., 2000, GrandPre et al., 2000; Fournier et al., 2001). The role of astrocytes in this process was proposed but remains incompletely understood (Silver and Miller, 2004). Astrocyte activation (reactive gliosis) accompanies neurotrauma, stroke, neurodegenerative diseases, or tumors. Two prominent hallmarks of reactive gliosis are hypertrophy of astrocytic processes and upregulation of intermediate filaments. Using the entorhinal cortex lesion model in mice, we found that reactive astrocytes devoid of the intermediate filament proteins glial fibrillary acidic protein and vimentin (GFAP-/-Vim-/-), and consequently lacking intermediate filaments (Colucci-Guyon et al., 1994; Pekny et al., 1995; Eliasson et al., 1999), showed only a limited hypertrophy of cell processes. Instead, many processes were shorter and not straight, albeit the volume of neuropil reached by a single astrocyte was the same as in wild-type mice. This was accompanied by remarkable synaptic regeneration in the hippocampus. On a molecular level, GFAP-/-Vim-/- reactive astrocytes could not upregulate endothelin B receptors, suggesting that the upregulation is intermediate filament dependent. These findings show a novel role for intermediate filaments in astrocytes and implicate reactive astrocytes as potent inhibitors of neuroregeneration.
|
|
