| 1. |
|
|
| 2. |
- Ström, Åsa, et al.
(författare)
-
Involvement of the CD1d-Natural killer T cell pathway in neointima formation after vascular injury
- 2007
-
Ingår i: CIRCULATION RESEARCH. - 0009-7330. ; 101:8
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies have established that the immune system plays an important role in the development of atherosclerosis. However, its role in regulating the arterial response to mechanical injury is less well studied. Arterial injury is associated with local accumulation of antibodies, and mice lacking functional T and B cells exhibit increased neointima formation, indicating that adaptive immune responses to neoantigens in the damaged tissue modulate the vascular repair process. To study the role of lipid antigen presentation in the arterial response to injury, we analyzed neointima formation in mice deficient in the lipid antigen-presenting molecule CD1d using a carotid collar model. As compared with control mice, neointima formation was reduced by >60% (P<0.01) in CD1d-/- mice. Moreover, carotid injury of wild-type C57BL/6 mice was associated with expansion of CD1d-restricted natural killer T cells in the spleen and accumulation of natural killer T cells in the periadventitial space of injured arteries. The results suggest that presentation of lipid antigens through the CD1d-natural killer T cell pathway modulates vascular repair responses.
|
|
| 3. |
- Guy, Jodie E, et al.
(författare)
-
New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2.
- 2008
-
Ingår i: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 381:4, s. 941-55
-
Tidskriftsartikel (refereegranskat)abstract
- Human MCFD2 (multiple coagulation factor deficiency 2) is a 16-kDa protein known to participate in transport of the glycosylated human coagulation factors V and VIII along the secretory pathway. Mutations in MCFD2 or in its binding partner, the membrane-bound transporter ERGIC (endoplasmic reticulum-Golgi intermediate compartment)-53, cause a mild form of inherited hemophilia known as combined deficiency of factors V and VIII (F5F8D). While ERGIC-53 is known to be a lectin-type mannose binding protein, the role of MCFD2 in the secretory pathway is comparatively unclear. MCFD2 has been shown to bind both ERGIC-53 and the blood coagulation factors, but little is known about the binding sites or the true function of the protein. In order to facilitate understanding of the function of MCFD2 and the mechanism by which mutations in the protein cause F5F8D, we have determined the structure of human MCFD2 in solution by NMR. Our results show the folding of MCFD2 to be dependent on availability of calcium ions. The protein, which is disordered in the apo state, folds upon binding of Ca(2+) to the two EF-hand motifs of its C-terminus, while retaining some localized disorder in the N-terminus. NMR studies on two disease-causing mutant variants of MCFD2 show both to be predominantly disordered, even in the presence of calcium ions. These results provide an explanation for the previously observed calcium dependence of the MCFD2-ERGIC-53 interaction and, furthermore, clarify the means by which mutations in this protein result in inefficient secretion of blood coagulation factors V and VIII.
|
|
| 4. |
|
|
| 5. |
- Neil, Maria, et al.
(författare)
-
Body composition and muscle glycogen contents of piglets of sows fed diets differing in fatty acids profile and contents
- 2009
-
Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413 .- 1878-0490. ; 123, s. 329-334
-
Tidskriftsartikel (refereegranskat)abstract
- To study the influence of sow dietary fat on piglet body characteristics, multiparous sows were allocated to one of four different dietary treatments: a conventional low fat (3%) diet (LF) and three high fat (6%) diets; high fat saturated (HFS), high fat oats (HFO), and high fat linseed (HFL). All sows were fed the allocated diet from weaning of the preceding litter until the day after farrowing. At farrowing, one liveborn piglet per litter (NB). was sacrificed and dissected immediately after birth. The heaviest (H) and the lightest (L) piglets in the litter were killed and dissected in the same manner at one day of age. Measurement of body length and circumference, organ weight, body chemical composition and muscle glycogen content were determined. Body measurements were adjusted to the mean body weight (1.67 kg). Dietary treatment did not have any significant influence on body components or carcass traits except for lung weight, being lower in HFO and HFL than in LF piglets. Piglet category affected almost all parameters considered, showing the lowest values for NB piglets, except for lung and circumference that were higher in NB than in L and H piglets: and length which was lower in NB than in L piglets. NB piglets had the highest amount of muscle glycogen content. no difference was found between H and L piglets. Dietary treatments influenced piglet chemical composition, showing the highest overall values of dry matter (DM). protein, and fat for the HFL piglets' carcasses. The present data provide additional information on the depletion of energy reserves; it would appear that sow dietary fat has relatively little effect on progeny since only body chemical composition was significantly influenced by HFL diet. (C) 2008 Elsevier B.V. All rights reserved.
|
|
| 6. |
- Nilsson, Jan, et al.
(författare)
-
Regulatory T cells and the control of modified lipoprotein autoimmunity-driven atherosclerosis.
- 2009
-
Ingår i: Trends in Cardiovascular Medicine. - : Elsevier BV. - 1873-2615 .- 1050-1738. ; 19:8, s. 272-276
-
Tidskriftsartikel (refereegranskat)abstract
- It has long been recognized that arterial inflammation plays a key role in the development of atherosclerosis. More recent evidence has suggested that this inflammation is modulated by autoimmune responses against modified self-antigens, such as oxidized low-density lipoprotein, in the vascular wall. However, the role of the immune system in atherosclerosis appears to be more complex than in classic autoimmune diseases; and a number of protective immune responses have also been identified. One of the most important of these is carried out by the regulatory T cells. Regulatory T cells inhibit the development of autoimmunity by controlling the activity of autoreactive T cells. If the function of regulatory T cells is compromised in hypercholesterolemic mouse models of atherosclerosis, the development of disease becomes much more aggressive. In this review, we will discuss the possibility that the inflammatory activity in atherosclerotic lesions depends on the balance between plaque antigen-specific proinflammatory Th1-type T cells and anti-inflammatory regulatory T cells specific for the same antigen. We will also discuss the role of hypercholesterolemia in generation of these modified self-antigens as well as ongoing research aiming to develop novel immune-modulating therapy for prevention of cardiovascular disease by targeting these processes.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Wigren, Maria, et al.
(författare)
-
Atheroprotective effects of Alum are associated with capture of oxidized LDL antigens and activation of regulatory T cells
- 2009
-
Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 104:12, s. e62-70
-
Tidskriftsartikel (refereegranskat)abstract
- The immune system represents a promising novel target for prevention of atherosclerosis. Several pilot vaccines that reduce atherosclerosis in experimental animals have been developed. The aluminum hydroxide adjuvant Alum has been shown to have antiatherogenic properties in itself, suggesting that it may be a suitable adjuvant in possible future atherosclerosis vaccines. To characterize the immune pathways mediating this protection, we treated wild-type C57BL/6 and Apoe(-)(/)(-) mice with Alum or PBS. Analyses of splenocytes isolated from 12-week-old mice demonstrated that Alum increased the presence of CD4(+)CD25(+)FoxP3(+) regulatory T cells and downregulated the expression of T cell activation markers CD28 and ICOS in Apoe(-)(/)(-) mice but not in C57BL/6 wild-type mice. A similar immunosuppressive phenotype was found also in 25-week-old Apoe(-)(/)(-) mice and was associated with reduced atherosclerosis. Alum precipitates recovered from the injection site of Apoe(-)(/)(-) mice contained antigens derived from oxidized LDL. These findings demonstrate that treatment of Apoe(-)(/)(-) mice with Alum results in an increase of regulatory T cells and suggest that these are activated by tolerogenic antigen-presenting cells presenting oxidized LDL antigens. Our findings provide improved mechanistic understanding of the atheroprotective properties of aluminum hydroxide adjuvants but also point to the importance of determining if hypercholesterolemia may compromise the efficacy of Alum-containing vaccines used clinically today.
|
|
| 10. |
|
|
