The clinical dynamic changes of macrophage phenotype and function in different stages of human wound healing and hypertrophic scar formation

The clinical dynamic changes of macrophage phenotype and function in different stages of human wound healing and hypertrophic scar formation
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人体伤口愈合和增生性疤痕形成不同阶段巨噬细胞表型和功能的临床动态变化

DOI:
10.1111/iwj.13041
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发表时间:
2019-04-01
影响因子:
3.1
通讯作者:
Su, Yingjun
Su, Yingjun
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Lin;Wang, Jianzhang;Su, Yingjun

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增生性瘢痕(hypertrophic scar,HS)的发病机制至今仍不清楚。巨噬细胞,特别是M1或M2的极化,在控制瘢痕形成程度方面起着关键作用。在伤口愈合和HS形成的长期期间,人类样本中巨噬细胞表型的分析可以为理解人类瘢痕的病理学提供有价值的临床证据。采集人伤口和HS标本,通过免疫荧光鉴定巨噬细胞表型,并通过RT-PCR检测与M1和M2巨噬细胞相关的生物标志物和细胞因子。通过线性回归分析巨噬细胞表型和HS特征之间的相关性。我们发现在早期伤口组织中,M1巨噬细胞在真皮浅层的血管周围过度且持续浸润,而M2巨噬细胞在后期伤口组织和HS的增殖期中占主导地位,并分散在整个真皮中。M1巨噬细胞的密度与肿瘤坏死因子-α(TNF-α)和IL-6的mRNA表达水平呈正相关。M2巨噬细胞密度与ARG 1呈正相关,与HS持续时间呈负相关。证实了M1巨噬细胞和M2巨噬细胞在人伤口和HS组织中的顺序浸润。
The pathogenesis of hypertrophic scar (HS) is still poorly understood. Macrophages, especially the polarisation of that to M1 or M2, play a pivotal role in control of the degree of scar formation. Profiling of macrophage phenotypes in human specimens during long‐term period of wound healing and HS formation may provide valuable clinical evidence for understanding the pathology of human scars. Human wound and HS specimens were collected, the macrophage phenotype was identified by immunofluorescence, and biomarkers and cytokines associated with M1 and M2 macrophages were detected by RT‐PCR. The correlation between the macrophage phenotype and HS characteristics was analysed by linear regression analyses. We found excessive and persistent infiltration by M1 macrophages around the blood vessels in the superficial layer of the dermis at early wound tissues, whereas M2 macrophages predominated in later wound tissues and the proliferative phase of HS and were scattered throughout the dermis. The density of M1 macrophages was positively correlated with mRNA expression levels of tumour necrosis factor‐alpha (TNF‐α) and IL‐6. The density of M2 macrophages was positively correlated with ARG1 and negatively correlated with the duration of HS. The sequential infiltration by M1 macrophage and M2 macrophages in human wound and HS tissues was confirmed.