| 1. |
- Horger, B A, et al.
(författare)
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Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons
- 1998
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 18:13, s. 4929-4937
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Tidskriftsartikel (refereegranskat)abstract
- Glial cell line-derived neurotrophic factor (GDNF) exhibits potent effects on survival and function of midbrain dopaminergic (DA) neurons in a variety of models. Although other growth factors expressed in the vicinity of developing DA neurons have been reported to support survival of DA neurons in vitro, to date none of these factors duplicate the potent and selective actions of GDNF in vivo. We report here that neurturin (NTN), a homolog of GDNF, is expressed in the nigrostriatal system, and that NTN exerts potent effects on survival and function of midbrain DA neurons. Our findings indicate that NTN mRNA is sequentially expressed in the ventral midbrain and striatum during development and that NTN exhibits survival-promoting actions on both developing and mature DA neurons. In vitro, NTN supports survival of embryonic DA neurons, and in vivo, direct injection of NTN into the substantia nigra protects mature DA neurons from cell death induced by 6-OHDA. Furthermore, administration of NTN into the striatum of intact adult animals induces behavioral and biochemical changes associated with functional upregulation of nigral DA neurons. The similarity in potency and efficacy of NTN and GDNF on DA neurons in several paradigms stands in contrast to the differential distribution of the receptor components GDNF Family Receptor alpha1 (GFRalpha1) and GFRalpha2 within the ventral mesencephalon. These results suggest that NTN is an endogenous trophic factor for midbrain DA neurons and point to the possibility that GDNF and NTN may exert redundant trophic influences on nigral DA neurons acting via a receptor complex that includes GFRalpha1.
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| 2. |
- Cohn, L, et al.
(författare)
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Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentation
- 2013
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 210:5, s. 1049-1063
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Tidskriftsartikel (refereegranskat)abstract
- Human BDCA3+ dendritic cells (DCs), the proposed equivalent to mouse CD8α+ DCs, are widely thought to cross present antigens on MHC class I (MHCI) molecules more efficiently than other DC populations. If true, it is unclear whether this reflects specialization for cross presentation or a generally enhanced ability to present antigens on MHCI. We compared presentation by BDCA3+ DCs with BDCA1+ DCs using a quantitative approach whereby antigens were targeted to distinct intracellular compartments by receptor-mediated internalization. As expected, BDCA3+ DCs were superior at cross presentation of antigens delivered to late endosomes and lysosomes by uptake of anti-DEC205 antibody conjugated to antigen. This difference may reflect a greater efficiency of antigen escape from BDCA3+ DC lysosomes. In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1+ DCs were as efficient at cross presentation as BDCA3+ DCs. Because BDCA3+ DCs and BDCA1+ DCs were also equivalent at presenting peptides and endogenously synthesized antigens, BDCA3+ DCs are not likely to possess mechanisms for cross presentation that are specific to this subset. Thus, multiple DC populations may be comparably effective at presenting exogenous antigens to CD8+ T cells as long as the antigen is delivered to early endocytic compartments.
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