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Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
Long-term persistence of human donor alveolar macrophages in lung transplant recipients
Ibon Eguíluz-Gracia1, Hans Henrik Lawaetz Schultz2, Liv I B Sikkeland3
1Department of Pathology, Center for Immune Regulation (CIR), Oslo University Hospital-Rikshospitalet and University of Oslo, Oslo, Norway.
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 100 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 2 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.
Insights
Human alveolar macrophages (AMFs) persist for years after lung transplantation, originating from both donor cells and recipient monocytes. This self-renewal capacity suggests potential therapeutic applications for lung diseases.
Area of Science:
- Immunology
- Cell Biology
- Transplantation Science
Background:
- Alveolar macrophages (AMFs) are crucial for lung function and may influence lung transplant outcomes.
- The origin and lifespan of human AMFs remain largely unknown, unlike findings in animal models suggesting embryonic self-maintenance.
Purpose of the Study:
- To investigate the origin and longevity of human alveolar macrophages (AMFs) in lung transplant recipients.
- To assess AMF development in a humanized mouse model for insights into human AMF ontogeny.
Main Methods:
- Utilized transbronchial biopsies from 10 lung transplant patients over 100 weeks.
- Employed combined in situ hybridization for X/Y chromosomes and immunofluorescence for macrophage markers.
- Assessed AMF development in humanized mice reconstituted with CD34+ umbilical cord-derived cells.
Main Results:
- Donor-derived AMFs remained stable for two years post-transplantation, with evidence of local proliferation indicating self-renewal.
- Humanized mouse lungs showed abundant human AMFs originating from monocytes.
- Recipient monocytes were observed to populate alveoli early post-transplantation, differentiating into mature, proliferating AMFs, leading to stable mixed chimerism.
Conclusions:
- Human AMFs persist in the lung for several years, suggesting pulmonary macrophage transplantation as a viable therapy for AMF dysfunction.
- Long-term persistence of donor AMFs in lung transplantation may play a role in chronic graft rejection development.
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