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Titolo:
Modification of the genetic program of human alveolar macrophages by adenovirus vectors in vitro is feasible but inefficient, limited in part by the low level of expression of the coxsackie/adenovirus receptor
Autore:
Kaner, RJ; Worgall, S; Leopold, PL; Stolze, E; Milano, E; Hidaka, C; Ramalingam, R; Hackett, NR; Singh, R; Bergelson, J; Finberg, R; Falck-Pedersen, E; Crystal, RG;
Indirizzi:
CornellYUniv, Med Ctr, New York Hosp, Div Pulm & Crit Care Med, New York, N Cornell Univ New York NY USA 10021 Div Pulm & Crit Care Med, New York, N Cornell Univ, Coll Med, Dept Microbiol, New York, NY USA Cornell Univ NewYork NY USA Coll Med, Dept Microbiol, New York, NY USA Childrens04osp Philadelphia, Div Immunol & Infect Dis, Philadelphia, PA 191 Childrens Hosp Philadelphia Philadelphia PA USA 19104 hiladelphia, PA 191 Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA Dana Farber Canc Inst Boston MA USA 02115 nfect Dis, Boston, MA 02115 USA
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
fascicolo: 3, volume: 20, anno: 1999,
pagine: 361 - 370
SICI:
1044-1549(199903)20:3<361:MOTGPO>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHRONIC GRANULOMATOUS-DISEASE; MONOCYTE-DERIVED MACROPHAGES; HUMAN CFTR CDNA; REPLICATION-DEFICIENT; RESPIRATORY-TRACT; CYSTIC-FIBROSIS; IN-VIVO; RECOMBINANT ADENOVIRUSES; EPITHELIAL SURFACE; IMMUNE-RESPONSES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Kaner, RJ CornellSt,ST505,d Ctr, New York Hosp, Div Pulm & Crit Care Med, 520 E 70th Cornell Univ 520 E 70th St,ST505 New York NY USA 10021 20 E 70th
Citazione:
R.J. Kaner et al., "Modification of the genetic program of human alveolar macrophages by adenovirus vectors in vitro is feasible but inefficient, limited in part by the low level of expression of the coxsackie/adenovirus receptor", AM J RESP C, 20(3), 1999, pp. 361-370

Abstract

Robust expression of genes transferred by adenovirus (Ad) vectors depends upon efficient entry of vectors into target cells. Cells deficient in the coxsackie/adenovirus receptor (CAR) are difficult targets for Ad-mediated gene transfer. We hypothesized that low levels of CAR expression may be responsible, in part, for the relative inefficiency of Ad-mediated gene transferto human alveolar macrophages (AMs). CAR gene expression was detected in human AMs by reverse transcription-polymerase chain reaction and at low levels by Northern analysis. Indirect immunofluorescence showed specific, low-intensity surface staining for CAR, but at levels below those found on the positive-control A549 human lung epithelial cell line. Consistent with this,AMs expressed Ad vector transgenes 100 to 1,000-fold less efficiently thanA549 cells, as assessed using the beta-galactosidase reporter (chemiluminescence assay) and green fluorescent protein (fluorescence microscopy and flow cytometry). At high multiplicity of infection, AMs from an HIV+ individual could be transduced with an AdIFN gamma vector to secrete detectable human interferon-gamma. Ad transgene expression by AMs was blocked by capsid fiber protein, suggesting that CAR is required in the pathway for productiveAd entry into alveolar macrophages. To confirm that Ad transgene expression by AMs is limited by low levels of CAR expression, cells were infected with an Ad vector containing the CAR complementary DNA (cDNA). Enhanced expression of CAR protein was demonstrated by indirect immunofluorescence, and the CAR cDNA-transduced cells showed 5-fold enhancement of subsequent Ad transgene expression. These observations demonstrate that human AMs can be targets for Ad-mediated gene transfer, but that efficiency of transgene expression is limited, at least in part, by low levels of CAR expression.

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Documento generato il 26/09/20 alle ore 02:17:35