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Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse
J Hopkinson-Woolley1, D Hughes, S Gordon
1Department of Human Anatomy, Oxford University, UK.
Abstract:
Macrophages play a pivotal role in the adult inflammatory response to wounding. They are directly responsible for cellular debridement and, by providing a source of growth factors and cytokines, they recruit other inflammatory and fibroblastic cells and influence cell proliferation and tissue remodelling. In this paper we investigate the role of macrophages in clearing areas of programmed cell death in the developing embryo and also their role in embryonic and foetal wound healing. Immunocytochemistry using the monocyte/macrophage-specific monoclonal antibody, F4/80, reveals a close association between areas of programmed cell death in the remodelling interdigital regions of the mouse footplate and of F4/80-positive cells, suggesting that monocyte-derived macrophages, and not locally recruited fibroblastic cells, as previously believed, are responsible for phagocytosing and clearing areas of interdigital apoptosis. Our studies of wound healing reveal that macrophages are not recruited to, and therefore cannot be playing an active role in the healing of, excisional wounds made in the mouse embryo at any stage up until E14.5. Beyond this transition stage we see a significant recruitment of macrophages within 12 hours of wounding. We find that macrophages can be attracted to wounds in earlier embryos if the wound results in significant cell death such as after burning.
Insights
Macrophages clear cellular debris during embryonic development and wound healing. In embryos, these cells phagocytose apoptotic cells and aid wound repair after embryonic day 14.5, especially when cell death is significant.
Area of Science:
- Developmental biology
- Immunology
- Wound healing research
Background:
- Macrophages are crucial for adult inflammatory responses and tissue remodeling.
- Their role in embryonic development, specifically in clearing programmed cell death and wound healing, is not fully understood.
Purpose of the Study:
- To investigate the role of macrophages in clearing programmed cell death in developing mouse embryos.
- To examine the function of macrophages in embryonic and fetal wound healing.
Main Methods:
- Utilized immunocytochemistry with the F4/80 antibody to identify macrophages.
- Created excisional wounds in mouse embryos at various developmental stages.
- Analyzed macrophage recruitment and activity in response to programmed cell death and wounding.
Main Results:
- Macrophages (F4/80-positive cells) were found to be closely associated with areas of programmed cell death in embryonic interdigital regions, suggesting they phagocytose apoptotic cells.
- Macrophages were not recruited to excisional wounds in mouse embryos before embryonic day 14.5.
- Significant macrophage recruitment occurred within 12 hours of wounding in embryos after embryonic day 14.5.
- Macrophages were attracted to earlier embryonic wounds if the injury caused significant cell death, such as from burning.
Conclusions:
- Monocyte-derived macrophages, not fibroblastic cells, are responsible for clearing interdigital apoptosis during mouse embryonic development.
- Macrophages play a critical role in embryonic wound healing primarily after embryonic day 14.5.
- Macrophage recruitment to embryonic wounds is dependent on the presence of significant cell death.