Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation.
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.
Aliotta
Jason M
JM
Division of Hematology and Oncology, Rhode Island Hospital, 3rd Floor, George Building, 593 Eddy Street, Providence, Rhode Island 02903, USA. jason_aliotta@brown.edu
Sanchez-Guijo
Fermin M
FM
Dooner
Gerri J
GJ
Johnson
Kevin W
KW
Dooner
Mark S
MS
Greer
Kenneth A
KA
Greer
Deborah
D
Pimentel
Jeffrey
J
Kolankiewicz
Luiz M
LM
Puente
Napoleon
N
Faradyan
Sam
S
Ferland
Paulette
P
Bearer
Elaine L
EL
Passero
Michael A
MA
Adedi
Mehrdad
M
Colvin
Gerald A
GA
Quesenberry
Peter J
PJ
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*
D017077:Culture Media, Conditioned; D012333:RNA, Messenger