Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we demonstrate that the cells which initiate replication of Epstein-Barr virus (EBV) in the tonsils of healthy carriers are plasma cells (CD38hi, CD10-, CD19+, CD20lo, surface immunoglobulin negative, and cytoplasmic immunoglobulin positive). We further conclude that differentiation into plasma cells, and not the signals that induce differentiation, initiates viral replication. This was confirmed by in vitro studies showing that the promoter for BZLF1, the gene that begins viral replication, becomes active only after memory cells differentiate into plasma cells and is also active in plasma cell lines. This differs from the reactivation of BZLF1 in vitro, which occurs acutely and is associated with apoptosis and not with differentiation. We suggest that differentiation and acute stress represent two distinct pathways of EBV reactivation in vivo. The fraction of cells replicating the virus decreases as the cells progress through the lytic cycle such that only a tiny fraction actually release infectious virus. This may reflect abortive replication or elimination of cells by the cellular immune response. Consistent with the later conclusion, the cells did not down regulate major histocompatibility complex class I molecules, suggesting that this is not an immune evasion tactic used by EBV and that the cells remain vulnerable to cytotoxic-T-lymphocyte attack.
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PMID:Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. 1561 56

Neutral endopeptidase is a membrane bound enzyme with various functions depending on cell type or tissue origin. Normal development and differentiation of immature B lymphocytes depends on expression of CD10/NEP on B cell progenitors and bone marrow stromal cells. Synthetic glucocorticoid dexamethasone (dex), an immunosuppressive and anti-inflammatory drug, was shown to be a potent modulator of CD10/NEP expressed on cells of non-hematopoietic origin. We investigated the effect of dex on expression of differentiation marker CD10/NEP on immature B cells. The drug was applied in concentrations corresponding to the physiological range. CD10/NEP was measured at three levels of expression: mRNA (by means of duplex PCR), membrane protein marker (FACS analysis) and enzyme activity (hydrolysis of a selective chromogenic substrate). Dex down-regulated CD10/NEP expression on immature B cell line NALM-6 in a concentration- and time-dependent fashion. The effect was detected at all three levels. Dex-induced CD10/NEP down-regulation was mediated via glucocorticoid receptors (GR), as it was fully abrogated by a GR antagonist, RU 38486. That occurred at all three levels. The mechanism of dex-induced CD10/NEP down-regulation is not likely to include selection of cells that are CD10low since the effect was partly reversible after the removal of dex. However, dex-induced CD10/NEP down-regulation did include decreased transcription of the CD10 mRNA. Transcriptional inhibitor actinomycin D completely abolished dex-induced CD10/NEP down-regulation. Since differentiation of normal B lymphocytes is associated with down-regulation of CD10/NEP, the data presented suggest that low, physiologically relevant concentrations of glucocorticoids (such as observed in acute stress) may play a regulatory role in normal development and maturation of B lymphocytes.
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PMID:Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11; CD10) on immature B lymphocytes by dexamethasone. 1587 Sep 9