title: Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation.
abstract: Numerous animal studies have demonstrated that adult marrow-derived cells can contribute to the cellular component of the lung. Lung injury is a major variable in this process; however, the mechanism remains unknown. We hypothesize that injured lung is capable of inducing epigenetic modifications of marrow cells, influencing them to assume phenotypic characteristics of lung cells. We report that under certain conditions, radiation-injured lung induced expression of pulmonary epithelial cell-specific genes and prosurfactant B protein in cocultured whole bone marrow cells separated by a cell-impermeable membrane. Lung-conditioned media had a similar effect on cocultured whole bone marrow cells and was found to contain pulmonary epithelial cell-specific RNA-filled microvesicles that entered whole bone marrow cells in culture. Also, whole bone marrow cells cocultured with lung had a greater propensity to produce type II pneumocytes after transplantation into irradiated mice. These findings demonstrate alterations of marrow cell phenotype by lung-derived microvesicles and suggest a novel mechanism for marrow cell-directed repair of injured tissue.
authors.affiliation: Division of Hematology and Oncology, Rhode Island Hospital, 3rd Floor, George Building, 593 Eddy Street, Providence, Rhode Island 02903, USA. jason_aliotta@brown.edu
authors.forename: Jason M
authors.initials: JM
authors.lastname: Aliotta
authors.forename: Fermin M
authors.initials: FM
authors.lastname: Sanchez-Guijo
authors.forename: Gerri J
authors.initials: GJ
authors.lastname: Dooner
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Johnson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Dooner
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Greer
authors.forename: Deborah
authors.initials: D
authors.lastname: Greer
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pimentel
authors.forename: Luiz M
authors.initials: LM
authors.lastname: Kolankiewicz
authors.forename: Napoleon
authors.initials: N
authors.lastname: Puente
authors.forename: Sam
authors.initials: S
authors.lastname: Faradyan
authors.forename: Paulette
authors.initials: P
authors.lastname: Ferland
authors.forename: Elaine L
authors.initials: EL
authors.lastname: Bearer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Passero
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Adedi
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Colvin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quesenberry
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D018874:Spheroids, Cellular / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D012333:RNA, Messenger