engleski

Surveillence of Neuro-Immunological Liaison by NF-kB Activation in Different Cell Types

Although considered as an immune privileged site, a tight functional link between Central Nervous System and Peripheral Immune System closely related to the activity of NF-kB transcription factor has been evidenced in numerous brain pathological conditions.One of the most instructive example is prion neuroinvasion and development of transmissible spongiform encephalopathy (TSE) or prion disease. The failure of peripherally administered prions to elicit disease in immune-deficient mice indicates that this is crucial for TSE pathogenesis and it seems to go through topographic relations between follicular dendritic cells (FDC) and sympathetic endings in lymphoid organs. The new insight into the molecular requirements for follicular stromal cell and FDC development in NF-kB p52 deficient mice highlights the role of NF-kB transcription factor in prion disease progression. FDCs which accumulate disease associated prion proteins are totally absent from p52 deficient animals, which may not be so surprising givent the fact that these cells express high p52 level. Furthermore, adoptive transfer of wild type bone marrow cells (NF-kB +/+ background) into p52 deficent animals (NF-kB -/- background) did not correct the FDC defect but did result in the appearance of MOMA-1+ metallophilic macrophages, which seem to be precursor cells for the development of MOMA-1+ perivascular macropahges located in the immediate vicinity of the blood brain barrier (BBB). Perivascular macrophages represent the major pool of cells which become quickly replenished follwoing hypoxic stress or inflammation. How the lack of NF-kB activity within this cellular compartment influnces this response is not clear. RT-PCR analysis of the expression level of mRNA for LT alpha, LT beta, TNFRI and BLC of the splenic cells from p52/NF-kB mutant/wt BM chimera did not reveal major changes compared to wt/wt BM chimeras, indicating that their normal expression within splenic tissue does not assure for complete restoration of FDC network in p52/NF-kB mutant. Enriched population of wild type FDCs express all of these molecules, which implies that in case of p52/NF-kB mice, their normal production by hematopoietically derived clls is not sufficient enough to ensure normal FDC development. This would further indicate that the normal distance between FDCs and splenic nerve terminals in such mice is impaired. In the view of the fact that prion neuroinvasion highly depends on physical distance between sympathetic nerve endings and FDC dendritic extensions, it is not hard to imagine that this could be the way to approach the problem of prion disease development.

NF-kB activation; sympathetic nerves; follicular dendritic cells; prion diseases

nije evidentirano