Macrophage depletion impairs corneal wound healing after autologous transplantation in mice.

Macrophage depletion impairs corneal wound healing after autologous transplantation in mice.
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巨噬细胞耗竭会损害小鼠自体移植后角膜伤口的愈合

DOI:
10.1371/journal.pone.0061799
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Shi W
Shi W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li S;Li B;Jiang H;Wang Y;Qu M;Duan H;Zhou Q;Shi W

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已显示巨噬细胞在伤口愈合过程中起关键作用。在本研究中,通过清除局部浸润的巨噬细胞来研究巨噬细胞在自体角膜移植后伤口愈合中的作用。采用Balb/c小鼠自体角膜移植模型诱导创面修复。通过结膜下注射含氯膦酸盐的脂质体(Cl 2 MDP-LIP)来消耗大分子。术后14 d,采用免疫组化和角膜整体包埋染色法检测角膜组织中CD 11b + F4/80+巨噬细胞、α-平滑肌肌动蛋白+(α-SMA+)肌成纤维细胞、CD 31+血管内皮细胞和NG 2+周细胞的存在。从Balb/c小鼠中分离腹膜巨噬细胞,并将其输注到结膜中,以检查巨噬细胞耗竭对自体角膜移植后伤口愈合的恢复作用。结膜下注射Cl 2 MDP-LIP显著耗尽角膜驻留吞噬细胞并使巨噬细胞浸润到角膜基质中。与注射PBS-脂质体的小鼠相比,注射Cl 2 MDP-LIP的小鼠表现出较少的炎性细胞、不规则分布的细胞外基质、角膜上皮向基质内生长,甚至供体角膜与受体角膜分离。此外,巨噬细胞耗竭小鼠供体和受体角膜交界区的巨噬细胞、肌成纤维细胞、内皮细胞和周细胞的数量也减少。腹腔巨噬细胞输注可恢复巨噬细胞耗竭引起的角膜创面愈合缺陷。巨噬细胞耗竭通过至少部分影响血管生成和伤口闭合而显著损害自体角膜移植后的伤口愈合。
Macrophages have been shown to play a critical role in the wound healing process. In the present study, the role of macrophages in wound healing after autologous corneal transplantation was investigated by depleting local infiltrated macrophages. Autologous corneal transplantation model was used to induce wound repair in Balb/c mice. Macrophages were depleted by sub-conjunctival injections of clodronate-containing liposomes (Cl2MDP-LIP). The presence of CD11b+ F4/80+ macrophages, α-smooth muscle actin+ (α-SMA+) myofibroblasts, CD31+ vascular endothelial cells and NG2 + pericytes was examined by immunohistochemical and corneal whole-mount staining 14 days after penetrating keratoplasty. Peritoneal macrophages were isolated from Balb/c mice and transfused into conjunctiva to examine the recovery role of macrophages depletion on wound healing after autologous corneal transplantation. Sub-conjunctival Cl2MDP-LIP injection significantly depleted the corneal resident phagocytes and infiltrated macrophages into corneal stroma. Compared with the mice injected with PBS-liposome, the Cl2MDP-LIP-injected mice showed few inflammatory cells, irregularly distributed extracellular matrix, ingrowth of corneal epithelium into stroma, and even the detachment of donor cornea from recipient. Moreover, the number of macrophages, myofibroblasts, endothelial cells and pericytes was also decreased in the junction area between the donor and recipient cornea in macrophage-depleted mice. Peritoneal macrophages transfusion recovered the defect of corneal wound healing caused by macrophages depletion. Macrophage depletion significantly impairs wound healing after autologous corneal transplantation through at least partially impacting on angiogenesis and wound closure.
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发表时间: 2010-01-25
期刊: PloS one
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