Granule targeting of soluble tumor necrosis factor (TNF) receptor expressed during granulopoietic maturation in murine bone marrow cells.
Eur Cytokine Netw
; 17(2): 98-108, 2006 Jun.
Article
en En
| MEDLINE
| ID: mdl-16840028
ABSTRACT
In this experiment, we explored the potential of secretory lysosomes of hematopoietic cells to act as vehicles for immunomodulatory protein delivery at an inflammation site. We investigated whether exogenous soluble TNF-receptor 1 (sTNFR1) could be expressed in primary hematopoietic progenitor cells and become targeted for storage and secretion during granulopoietic differentiation. An sTNFR1 construct with a transmembrane domain (tm) and a cytosol sorting signal (Y) taken from CD63, was retrovirally transduced to lineage-negative murine hematopoietic bone marrow stem/progenitor cells. This process was followed by cytokine-driven granulopoietic maturation. The sTNFR1-tm-Y was found to be synthesized in precursor cells and to persist in mature granulocytes and monocytes/macrophages. Immunofluorescence-localization studies showed a granule pattern of sTNFR1-tm-Y in both precursor and mature granulocytes and secretion to phagosomes after ingestion of bacteria. Immunoelectron microscopy revealed co-localization between the sTNFR1-tm-Y and the primary (azurophil) granule marker myeloperoxidase. Collectively, our results demonstrated granule targeting, storage, and secretion of exogenous sTNFR1-tm-Y constitutively expressed during normal granulopoietic differentiation. These findings support the concept of using storage organelles of circulating hematopoietic cells as vehicles for targeting sites of inflammation with immunoregulatory agents.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoglobulina G
/
Células de la Médula Ósea
/
Diferenciación Celular
/
Receptores del Factor de Necrosis Tumoral
/
Gránulos Citoplasmáticos
/
Granulocitos
Límite:
Animals
Idioma:
En
Revista:
Eur Cytokine Netw
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Suecia