Disease relevance of Prg2

• In conclusion, MBP decreases epithelial barrier function and in this manner contributes to the pathogenesis of inflammatory bowel diseases [1].
• MBP-null mice were protected from inflammation associated with oxazolone colitis compared with wild-type mice [1].
• Human eosinophil major basic protein (MBP) is strongly implicated as a mediator of disease, especially bronchial asthma [2].
• B10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89-101 [3].
• We now report that in spinal cord sections of adult animals with active demyelination and inflammatory cells, in situ hybridization reveals a dramatic increase in probe binding to MBP-specific mRNA at 2-3 weeks after virus inoculation and before remyelination can be detected by morphological methods [4].

Psychiatry related information on Prg2

• In order to assess the role of idiotype (Id) and the anti-Id network in murine experimental autoimmune encephalomyelitis (EAE), Id-bearing monoclonal antibodies (mAb) to human myelin basic protein (MBP) peptide acetyl 1-9, as well as mAb anti-Id, were developed in EAE-susceptible PL/J mice (H-2u) [5].

High impact information on Prg2

• Transgenic mice were constructed expressing genes encoding a rearranged T cell receptor specific for myelin basic protein (MBP) [6].
• We have characterized TH cell reactivity in B10.PL and PL/J (H-2u) mice to 39 N-terminal MBP peptide derivatives of different lengths and with individual amino acid substitutions [7].
• Immunization with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease [8].
• To investigate when and where oligodendrocytes are first triggered to repair CNS myelin in such disease, we have used a complementary DNA probe specific for one major myelin protein gene, myelin basic protein (MBP), which hybridizes with the four forms of MBP messenger RNA in rodents [4].
• Our results suggest that in mice, glial cells react to a demyelinating process with widespread MBP mRNA synthesis which may be triggered by a diffusible factor released in the demyelinated areas [4].

Chemical compound and disease context of Prg2

• In this report we show that substituting alanines at all but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not alter its ability to bind A alpha uA beta u (MHC class II molecules), to stimulate specific T cells and, surprisingly, to induce experimental autoimmune encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice [9].
• The inclusion of physiological levels of UA in culture effectively inhibited ONOO(-)-mediated oxidation as well as tyrosine nitration, which has been associated with damage in EAE and multiple sclerosis, but had no inhibitory effect on the T cell-proliferative response to myelin basic protein (MBP) or on APC function [10].
• Desferrioxamine suppresses experimental allergic encephalomyelitis induced by MBP in SJL mice [11].

Biological context of Prg2

• The murine eosinophil major basic protein gene (Prg2) maps to chromosome 2 [12].
• The genomic structure and nucleotide sequence of the mMBP exons are well conserved with the human gene, although homology alignments of the encoded proteins show that extensive sequence conservation occurs only in the mature portion of the MBP molecules [13].
• The relationship between eosinophils and the development of Ag-induced pulmonary pathologies, including airway hyper-responsiveness, was investigated using mice deficient for the secondary granule component, major basic protein-1 (mMBP-1) [14].
• The gene encoding mMBP was isolated using a hMBP cDNA clone as a heterologous probe in low criteria screens of mouse genomic and cDNA libraries [13].
• Furthermore, OVA-specific T cells retained a naive phenotype and did not transcribe Th1 cytokines, in contrast to MBP-specific T cells [15].

Anatomical context of Prg2

• The thymus also plays a role in deletion of autoreactive T cells in the periphery following orally administered MBP [16].
• Overall, the oral administration of MBP has a profound effect on systemic immune responses, mediated largely by the generation of regulatory T cells that act to prevent or suppress EAE [16].
• Thus, in the absence of MBP, mice showed increased interleukin-10 (IL-10) production after stimulation of macrophages from the thoracic cavity where the worms reside [17].
• The autoimmune disease of the central nervous system (CNS), experimental allergic encephalomyelitis (EAE), is induced by challenge of genetically susceptible animals with spinal cord homogenates or myelin basic protein (MBP) [18].
• T cell clones were isolated from the mesenteric lymph nodes of SJL mice that had been orally tolerized to MBP [19].

Associations of Prg2 with chemical compounds

• Moreover, OVA sensitization/aerosol challenge of wild-type and mMBP-1(-/-) mice resulted in identical dose-response changes to either methacholine or serotonin [14].
• Both sensitization and allergen challenge resulted in an increase in the number of cells expressing major basic protein (MBP) (p < 0.05) [20].
• Eosinophil distribution was assessed using Scarlet Red stain and a polyclonal antibody recognizing eosinophil major basic protein (MBP) [21].
• The topology of the three epitopes implicates asparagine endopeptidase as the enzyme that controls recognition of this region of MBP [22].
• 14 of 18 (78%) NH2-terminal MBP-specific clones examined express a member of the TCR V beta 8 subfamily [23].

Other interactions of Prg2

• In addition, a genomic clone of mMBP-2 was isolated and this gene was shown to be physically linked to within 100 kb of mMBP-1 on the central region of mouse chromosome 2 [24].
• In this study, euthymic myelin basic protein (MBP) TCR transgenic mice are protected from EAE when fed MBP but are not protected when thymectomized [16].

Analytical, diagnostic and therapeutic context of Prg2

• Electron microscopy confirmed the presence of crystallized major basic protein (MBP) in the granules of some of these cells [25].
• Heparanase intracellular localization (confocal laser microscopy) and ability to bind to eosinophil major basic protein (MBP) were also evaluated (immunoprecipitation) [26].
• Moreover, using mMBP-1 knockout mice and immunohistochemistry with an antisera that recognizes both mMBP-1 and -2, we demonstrate that mMBP-2 protein expression is restricted to eosinophil lineage-committed cells [24].
• Immunofluorescence staining for MBP confirmed this distribution of eosinophils but also demonstrated some eosinophils in the maxillary sinuses and in circumscribed regions of the ethmoturbinates [21].
• Cell-free coculture supernatants contained a > or =5-kDa soluble factor that also diminished TER; these supernatants contained the eosinophil-granule proteins major basic protein (MBP) and eosinophil-derived neurotoxin (EDN) [1].

References