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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. LU ; Iversen, Martin; Andersen, Claus and Jahnsen, Frode L., et al. (2016) In Thorax 71(11). p.1006-1011
Abstract

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... (More)

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.

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publication status
published
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keywords
Lung Transplantation, Macrophage Biology, Pulmonary alveolar proteinosis
in
Thorax
volume
71
issue
11
pages
6 pages
publisher
BMJ Publishing Group
external identifiers
  • scopus:84977491481
  • wos:000386472500009
ISSN
0040-6376
DOI
10.1136/thoraxjnl-2016-208292
language
English
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yes
id
04afba30-57dc-4c93-9541-0100ecd1e31e
date added to LUP
2016-12-05 14:29:36
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2017-08-06 05:14:35
@article{04afba30-57dc-4c93-9541-0100ecd1e31e,
  abstract     = {<p>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.</p>},
  author       = {Eguíluz-Gracia, Ibon and Schultz, Hans Henrik Lawaetz and Sikkeland, Liv I B and Danilova, Elena and Holm, Are M. and Pronk, Cornelis J H and Agace, William W. and Iversen, Martin and Andersen, Claus and Jahnsen, Frode L. and Baekkevold, Espen S.},
  issn         = {0040-6376},
  keyword      = {Lung Transplantation,Macrophage Biology,Pulmonary alveolar proteinosis},
  language     = {eng},
  month        = {11},
  number       = {11},
  pages        = {1006--1011},
  publisher    = {BMJ Publishing Group},
  series       = {Thorax},
  title        = {Long-Term persistence of human donor alveolar macrophages in lung transplant recipients},
  url          = {http://dx.doi.org/10.1136/thoraxjnl-2016-208292},
  volume       = {71},
  year         = {2016},
}