Long-Term persistence of human donor alveolar macrophages in lung transplant recipients

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Long-Term persistence of human donor alveolar macrophages in lung transplant recipients. / Eguíluz-Gracia, Ibon; Schultz, Hans Henrik Lawaetz; Sikkeland, Liv I B; Danilova, Elena; Holm, Are M.; Pronk, Cornelis J H; Agace, William W.; Iversen, Martin; Andersen, Claus; Jahnsen, Frode L.; Baekkevold, Espen S.

In: Thorax, Vol. 71, No. 11, 01.11.2016, p. 1006-1011.

Research output: Contribution to journalArticle

Harvard

Eguíluz-Gracia, I, Schultz, HHL, Sikkeland, LIB, Danilova, E, Holm, AM, Pronk, CJH, Agace, WW, Iversen, M, Andersen, C, Jahnsen, FL & Baekkevold, ES 2016, 'Long-Term persistence of human donor alveolar macrophages in lung transplant recipients', Thorax, vol. 71, no. 11, pp. 1006-1011. https://doi.org/10.1136/thoraxjnl-2016-208292

APA

Eguíluz-Gracia, I., Schultz, H. H. L., Sikkeland, L. I. B., Danilova, E., Holm, A. M., Pronk, C. J. H., ... Baekkevold, E. S. (2016). Long-Term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax, 71(11), 1006-1011. https://doi.org/10.1136/thoraxjnl-2016-208292

CBE

Eguíluz-Gracia I, Schultz HHL, Sikkeland LIB, Danilova E, Holm AM, Pronk CJH, Agace WW, Iversen M, Andersen C, Jahnsen FL, Baekkevold ES. 2016. Long-Term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax. 71(11):1006-1011. https://doi.org/10.1136/thoraxjnl-2016-208292

MLA

Vancouver

Eguíluz-Gracia I, Schultz HHL, Sikkeland LIB, Danilova E, Holm AM, Pronk CJH et al. Long-Term persistence of human donor alveolar macrophages in lung transplant recipients. Thorax. 2016 Nov 1;71(11):1006-1011. https://doi.org/10.1136/thoraxjnl-2016-208292

Author

Eguíluz-Gracia, Ibon ; Schultz, Hans Henrik Lawaetz ; Sikkeland, Liv I B ; Danilova, Elena ; Holm, Are M. ; Pronk, Cornelis J H ; Agace, William W. ; Iversen, Martin ; Andersen, Claus ; Jahnsen, Frode L. ; Baekkevold, Espen S. / Long-Term persistence of human donor alveolar macrophages in lung transplant recipients. In: Thorax. 2016 ; Vol. 71, No. 11. pp. 1006-1011.

RIS

TY - JOUR

T1 - Long-Term persistence of human donor alveolar macrophages in lung transplant recipients

AU - Eguíluz-Gracia, Ibon

AU - Schultz, Hans Henrik Lawaetz

AU - Sikkeland, Liv I B

AU - Danilova, Elena

AU - Holm, Are M.

AU - Pronk, Cornelis J H

AU - Agace, William W.

AU - Iversen, Martin

AU - Andersen, Claus

AU - Jahnsen, Frode L.

AU - Baekkevold, Espen S.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background Alveolar macrophages (AMFs) are critical regulators of lung function, and may participate in graft rejection following lung transplantation. Recent studies in experimental animals suggest that most AMFs are self-maintaining cells of embryonic origin, but knowledge about the ontogeny and life span of human AMFs is scarce. Methods To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100â €..weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation for X/Y chromosomes and immunofluorescence staining for macrophage markers. Moreover, development of AMFs in humanised mice reconstituted with CD34+ umbilical cord-derived cells was assessed. Results The number of donor-derived AMFs was unchanged during the 2â €..year post-Transplantation period. A fraction of the AMFs proliferated locally, demonstrating that at least a subset of human AMFs have the capacity to self-renew. Lungs of humanised mice were found to abundantly contain populations of human AMFs expressing markers compatible with a monocyte origin. Moreover, in patients with lung transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period. Conclusions The finding that human AMFs are maintained in the lung parenchyma for several years indicates that pulmonary macrophage transplantation can be a feasible therapeutic option for patients with diseases caused by dysfunctional AMFs. Moreover, in a lung transplantation setting, long-Term persistence of donor AMFs may be important for the development of chronic graft rejection.

AB - Background Alveolar macrophages (AMFs) are critical regulators of lung function, and may participate in graft rejection following lung transplantation. Recent studies in experimental animals suggest that most AMFs are self-maintaining cells of embryonic origin, but knowledge about the ontogeny and life span of human AMFs is scarce. Methods To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100â €..weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation for X/Y chromosomes and immunofluorescence staining for macrophage markers. Moreover, development of AMFs in humanised mice reconstituted with CD34+ umbilical cord-derived cells was assessed. Results The number of donor-derived AMFs was unchanged during the 2â €..year post-Transplantation period. A fraction of the AMFs proliferated locally, demonstrating that at least a subset of human AMFs have the capacity to self-renew. Lungs of humanised mice were found to abundantly contain populations of human AMFs expressing markers compatible with a monocyte origin. Moreover, in patients with lung transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period. Conclusions The finding that human AMFs are maintained in the lung parenchyma for several years indicates that pulmonary macrophage transplantation can be a feasible therapeutic option for patients with diseases caused by dysfunctional AMFs. Moreover, in a lung transplantation setting, long-Term persistence of donor AMFs may be important for the development of chronic graft rejection.

KW - Lung Transplantation

KW - Macrophage Biology

KW - Pulmonary alveolar proteinosis

UR - http://www.scopus.com/inward/record.url?scp=84977491481&partnerID=8YFLogxK

U2 - 10.1136/thoraxjnl-2016-208292

DO - 10.1136/thoraxjnl-2016-208292

M3 - Article

VL - 71

SP - 1006

EP - 1011

JO - Thorax

T2 - Thorax

JF - Thorax

SN - 1468-3296

IS - 11

ER -