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Titolo:
Selective expansion of alveolar macrophages in vivo by adenovirus-mediatedtransfer of the murine granulocyte-macrophage colony-stimulating factor cDNA
Autore:
Worgall, S; Singh, R; Leopold, PL; Kaner, RJ; Hackett, NR; Topf, N; Moore, MAS; 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 MemNYloan Kettering Canc Ctr, James Ewing Lab Dev Hematopoiesis, New York,Mem Sloan Kettering Canc Ctr New York NY USA 10021 matopoiesis, New York,
Titolo Testata:
BLOOD
fascicolo: 2, volume: 93, anno: 1999,
pagine: 655 - 666
SICI:
0006-4971(19990115)93:2<655:SEOAMI>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCYTE-DERIVED MACROPHAGES; CHRONIC GRANULOMATOUS-DISEASE; GENE-TRANSFER; INTERFERON-GAMMA; IN-VIVO; REPLICATION-DEFICIENT; GROWTH-FACTOR; HUMAN-LUNG; GM-CSF; EXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Crystal, RG CornellSt,ST, Med Ctr, New York Hosp, Div Pulm & Crit Care Med, 520 E 70th Cornell Univ 520 E 70th St,ST 505 New York NY USA 10021 E 70th
Citazione:
S. Worgall et al., "Selective expansion of alveolar macrophages in vivo by adenovirus-mediatedtransfer of the murine granulocyte-macrophage colony-stimulating factor cDNA", BLOOD, 93(2), 1999, pp. 655-666

Abstract

Based on the hypothesis that genetic modification of freshly isolated alveolar macrophages (AM) with the granulocyte-macrophage colony-stimulating factor (GM-CSF) cDNA would induce AM to proliferate, this study focuses on the ability of adenoviral (Ad) vectors to transfer and efficiently express the murine (m) GM-CSF cDNA in murine AM with consequent expansion in the number of AM in vitro and in vivo. To demonstrate that an Ad vector can effectively transfer and express genes in AM, murine AM recovered by bronchoalveolar lavage from the lung of Balb/c mice were infected with an Ad vector coding for green fluorescent protein (GFP) in vitro and expressed GFP in a dose-dependent fashion. Infection of AM with an Ad vector containing an expression cassette coding for mGM-CSF led to GM-CSF expression and to AM proliferation in vitro. When AM infected with AdGFP were returned to the respiratory tract of syngeneic recipient mice, GFP-expressing cells could still be recovered by bronchoalveolar lavage 2 weeks later. In vitro infection of AM with AdmGM-CSF and subsequent transplantation of the genetically modified AMto the lungs of syngeneic recipients led to GM-CSF expression in vivo. Strikingly, the AM recovered by lavage 5 weeks after transplantation demonstrated an increased rate of proliferation, and the total number of alveolar macrophages was 1.9-fold greater than controls. importantly the increase in the numbers of AM was selective (ie, other inflammatory cell numbers were unchanged), end there was no modification to the lung architecture. Thus, it is feasible to genetically modify AM with Ad vectors and to use this strategy to modify the behavior of AM in vivo. Based on the importance of AM in the primary defense of the respiratory epithelial surface, this strategy maybe useful in enhancing pulmonary defenses in immunodeficiency states. (C) 1999 by The American Society of Hematology.

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Documento generato il 26/09/20 alle ore 01:39:52