engleski

Receptor-mediated down-regulation of neutral endopeptidase (NEP ; EC 3.4.24.11, CD10) on immature B lymphocytes by dexamethasone.

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 NEP/CD10 expressed on cells of nonhematopoietic origin. We investigated the effect of dexamethasone 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 (hydolysis of a selective chromogenic substrate). Dexamethasone 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 regulatory role in normal development and maturation of B-lymphocytes.

neutral endopeptidase; CD10; dexamethasone; glucocorticoid receptors; immature B lymphocytes; differentiation

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