| 1. |
- Cantoni, Claudia, et al.
(författare)
-
TREM2 regulates microglial cell activation in response to demyelination in vivo
- 2015
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 129:3, s. 429-447
-
Tidskriftsartikel (refereegranskat)abstract
- Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2(-/-)) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2(-/-) microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2(-/-) microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage.
|
|
| 2. |
- Oteng, Antwi-Boasiako, et al.
(författare)
-
Characterization of ANGPTL4 function in macrophages and adipocytes using Angptl4-knockout and Angptl4-hypomorphic mice[S]
- 2019
-
Ingår i: Journal of Lipid Research. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 0022-2275 .- 1539-7262. ; 60:10, s. 1741-1754
-
Tidskriftsartikel (refereegranskat)abstract
- Angiopoietin-like protein (ANGPTL)4 regulates plasma lipids, making it an attractive target for correcting dyslipidemia. However, ANGPTL4 inactivation in mice fed a high fat diet causes chylous ascites, an acute-phase response, and mesenteric lymphadenopathy. Here, we studied the role of ANGPTL4 in lipid uptake in macrophages and in the above-mentioned pathologies using Angptl4-hypomorphic and Angptl4(-/-) mice. Angptl4 expression in peritoneal and bone marrow-derived macrophages was highly induced by lipids. Recombinant ANGPTL4 decreased lipid uptake in macrophages, whereas deficiency of ANGPTL4 increased lipid uptake, upregulated lipid-induced genes, and increased respiration. ANGPTL4 deficiency did not alter LPL protein levels in macrophages. Angptl4-hypomorphic mice with partial expression of a truncated N-terminal ANGPTL4 exhibited reduced fasting plasma triglyceride, cholesterol, and NEFAs, strongly resembling Angptl4(-/-) mice. However, during high fat feeding, Angptl4-hypomorphic mice showed markedly delayed and attenuated elevation in plasma serum amyloid A and much milder chylous ascites than Angptl4(-/-) mice, despite similar abundance of lipid-laden giant cells in mesenteric lymph nodes. In conclusion, ANGPTL4 deficiency increases lipid uptake and respiration in macrophages without affecting LPL protein levels. Compared with the absence of ANGPTL4, low levels of N-terminal ANGPTL4 mitigate the development of chylous ascites and an acute-phase response in mice.
|
|
| 3. |
- Sandgren, B., et al.
(författare)
-
Assessment of wear and periacetabular osteolysis using dual energy computed tomography on a pig cadaver to identify the lowest acceptable radiation dose
- 2016
-
Ingår i: Bone & Joint Research. - : BRITISH EDITORIAL SOC BONE JOINT SURGERY. - 2046-3758. ; 5:7, s. 307-313
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Computed tomography (CT) plays an important role in evaluating wear and periacetabular osteolysis (PAO) in total hip replacements. One concern with CT is the high radiation exposure since standard pelvic CT provides approximately 3.5 millisieverts (mSv) of radiation exposure, whereas a planar radiographic examination with three projections totals approximately 0.5 mSv. The objective of this study was to evaluate the lowest acceptable radiation dose for dual-energy CT (DECT) images when measuring wear and periacetabular osteolysis in uncemented metal components. Materials and Methods A porcine pelvis with bilateral uncemented hip prostheses and with known linear wear and acetabular bone defects was examined in a third-generation multidetector DECT scanner. The examinations were performed with four different radiation levels both with and without iterative reconstruction techniques. From the high and low peak kilo voltage acquisitions, polychrmoatic images were created together with virtual monochromatic images of energies 100 kiloelectron volts (keV) and 150 keV. Results We could assess wear and PAO while substantially lowering the effective radiation dose to 0.7 mSv for a total pelvic view with an accuracy of around 0.5 mm for linear wear and 2 mm to 3 mm for PAO. Conclusion CT for detection of prosthetic wear and PAO could be used with clinically acceptable accuracy at a radiation exposure level equal to plain radiographic exposures.
|
|
