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Titolo:
INHIBITION OF CD10 NEUTRAL ENDOPEPTIDASE 24.11 PROMOTES B-CELL RECONSTITUTION AND MATURATION IN-VIVO
Autore:
SALLES G; RODEWALD HR; CHIN BS; REINHERZ EL; SHIPP MA;
Indirizzi:
HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY STBOSTON MA 02115 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY STBOSTON MA 02115 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT PATHOL BOSTON MA 02115 HARVARD UNIV,SCH MED,DEPT MED BOSTON MA 02115
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 16, volume: 90, anno: 1993,
pagine: 7618 - 7622
SICI:
0027-8424(1993)90:16<7618:IOCNE2>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
LYMPHOBLASTIC-LEUKEMIA ANTIGEN; SUBSTANCE-P; BONE-MARROW; CALLA; ENKEPHALINASE; LYMPHOPOIESIS; LUNG; TACHYKININS; PROGENITORS; POPULATION;
Keywords:
COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN; LYMPHOID PROGENITORS; DIFFERENTIATION; CELL SURFACE ENZYME;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
G. Salles et al., "INHIBITION OF CD10 NEUTRAL ENDOPEPTIDASE 24.11 PROMOTES B-CELL RECONSTITUTION AND MATURATION IN-VIVO", Proceedings of the National Academy of Sciences of the United Statesof America, 90(16), 1993, pp. 7618-7622

Abstract

The common acute lymphoblastic leukemia antigen [(CALLA) CD10, neutral endopeptidase 24.11 (NEP)] is a cell-surface zinc metalloprotease expressed by a subpopulation of early murine B-lymphoid progenitors and by bone marrow stromal cells that support the earliest stages of B lymphopoiesis. In previous in vitro studies in which uncommitted murine hematopoietic progenitors plated on a stromal cell layer differentiate into immature B cells, the inhibition of CD10/NEP increased early lymphoid colony numbers. To further characterize CD10/NEP function during lymphoid ontogeny in vivo, we utilized a Ly5 congenic mouse model in which the lymphoid differentiation of uncommitted hematopoietic progenitors from Ly5.1 donors was followed in sublethally irradiated Ly5.2 recipients treated with a specific long-acting CD10/NEP inhibitor arboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine (SCH32615)}. The expression of Ly5.1, B220, and surface IgM (sIgM) was utilized to characterizedonor-derived hematopoietic cells (Ly5.1+), B lymphocytes (B220+), and mature B cells (B220+ sIgM+) from the lymphoid organs of recipient animals treated with SCH32615 or vehicle alone. SCH32615-treated animals had higher percentages of Ly5.1+ donor splenocytes than animals treated with vehicle alone (16.9% vs. 10.4%, 63% increase, P = 0.013). Animals treated with the CD10/NEP inhibitor also had relatively more Ly5.1+ splenic B (B220+) cells than vehicle-treated animals (14.4% vs. 8.2%, 75% increase, P = 0.018). To more specifically characterize the effects of CD10/NEP inhibition on B-cell differentiation, Ly5.1+ splenocytes from animals treated with SCH32615 or vehicle alone were analyzed for coexpression of B220 and sIgM. Animals treated with the CD10/NFP inhibitor had a significantly higher percentage of mature donor B cells(Ly5.1+ B220+ sIgM+, 10.2% vs. 5.2%, 90% increase, P = 0.006) and a more modest relative increase in immature donor B cells (Ly5.1+ B220+ sIgM-, 4.7% vs. 3.4%, 38% increase, P = not significant). Taken together, these results suggest that CD10/NEP inhibition promotes the reconstitution and maturation of splenic B cells. Therefore, CD10/NEP may function to regulate B-cell ontogeny in vivo by hydrolyzing a peptide substrate that stimulates B-cell proliferation and/or differentiation.

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Documento generato il 27/11/20 alle ore 04:21:20