Monocyte M1/M2 profile is altered in paediatric burn patients with hypertrophic scarring. Issue 6 (17th July 2021)

• Record Type: Journal Article
• Authors: Williams, Helen; Suda, Sasithorn; Dervish, Suat; Yap, Yen Tien; Holland, Andrew J. A.; Medbury, Heather J.
• Is Part Of: Wound repair and regeneration. Volume 29:Issue 6(2021)
• Page Start: 996
• Page End: 1005
• Publication Date: 2021-07-17
• Subjects: burn -- flow cytometry -- monocytes -- scar; Wound healing -- Periodicals; Regeneration (Biology) -- Periodicals; 617.14
• DOI: 10.1111/wrr.12960
• Languages: English
• ISSNs: 1067-1927

Abstract

Abstract: Hypertrophic scars (HTS) remain a common outcome of burn injury, particularly in children. They can arise from variations in the wound healing stages, such as an excessive inflammatory response or inefficient remodelling. Of the cells contributing to these healing stages, macrophages and fibrocytes are crucial. Specifically, the inflammatory phase is dominated by M1 macrophages, the proliferation/remodelling stages by M2 macrophages, and scar tissue contains numerous fibrocytes. As the progenitors to these cells, monocytes, can also exhibit M1‐ and M2‐skewing, we proposed that their profile, or circulating fibrocyte counts, could be used to predict poor healing outcomes. To investigate this, we obtained blood samples from paediatric controls and burns patients, which were then divided into HTS and NoHTS groups upon scar assessment at 12 months. The samples were assessed by whole blood flow cytometry to quantify fibrocytes and monocyte subset proportions and to determine monocyte levels of M1 (CD86, CD120b, CD319) and M2 (CD93, CD163, CD200R) markers. Both burns groups had higher proportions of classical monocytes compared to controls, indicating increased cell turnover and/or entry of other subsets into the wound. In burns patients who took more than 21 days to heal, the HTS group had lower M2 (CD200R) expression with the ratio of M1/M2 (CD86/CD200R) being significantly higher. These results suggest an elevated early inflammatory monocyte response contributes to development of HTS. Correlations of marker expression with remaining healing time revealed a significant positive correlation with M1 (CD120b) and M1/M2 (CD120b/CD200R), suggesting a potential role for CD120b as an indicator of healing delay. Fibrocytes did not significantly differ between the groups. In conclusion, increased monocyte inflammation likely contributes to slower healing and development of scarring, but further studies are needed to determine the predictive power of monocyte inflammatory profile.