Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.
Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.
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DOI：
10.1371/journal.pone.0032333
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dudhia J
中科院分区：
文献类型：
--
作者：
Dakin SG;Werling D;Hibbert A;Abayasekara DR;Young NJ;Smith RK;Dudhia J
巨噬细胞（macrophages，M）在损伤的结缔组织中协调炎症和修复过程，但它们在肌腱愈合的不同阶段中的作用尚不清楚。我们研究了不同M亚群在自然发生的肌腱损伤的马模型中的贡献。从正常（未损伤）、亚急性（损伤后3-6周）和慢性损伤（损伤后>3个月）的浅趾屈肌腱收获死后组织。为了确定损伤肌腱中是否存在炎症，基于CD 172 a（泛M1 M）、CD 14高CD 206低（促炎M1 M）和CD 206高（抗炎M2M）的表面抗原表达对M1 M亚群进行定量，以评估潜在的极化表型。此外，脂氧素A4受体（FPR 2/ALX）用作缓解炎症的标志物。正常肌腱的M β和FPR 2/ALX均为阴性。相比之下，M1 M β在亚急性损伤中占主导地位，而在慢性损伤中观察到潜在的表型转换为M2M β极性。此外，FPR 2/ALX表达的肌腱细胞显着上调亚急性损伤，而不是慢性损伤。FPR 2/ALX配体膜联蛋白A1的表达在亚急性和慢性损伤中也显著增加，而在正常肌腱中表达水平较低。FPR 2/ALX表达减少和慢性损伤中M2M α表型的持续存在的组合表明肌腱损伤后炎症不完全消退的潜在机制。为了研究促炎介质对体外脂氧素A4（LXA 4）产生和FPR 2/ALX表达的影响，用白细胞介素-1 β和前列腺素E2刺激正常肌腱外植体。用任一介质刺激诱导LXA 4释放和72小时后FPR 2/ALX表达的最大上调。综上所述，我们的数据表明，虽然肌腱细胞能够安装一个保护机制，以抵消炎症刺激，这似乎是不足的持续时间和幅度在自然肌腱损伤，这可能会加强慢性炎症和纤维化修复，所示的存在M2 M β。
Macrophages (Mϕ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mϕ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3–6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mϕ sub-populations were quantified based on surface antigen expression of CD172a (pan Mϕ), CD14highCD206low (pro-inflammatory M1Mϕ), and CD206high (anti-inflammatory M2Mϕ) to assess potential polarised phenotypes. In addition, the Lipoxin A4 receptor (FPR2/ALX) was used as marker for resolving inflammation. Normal tendons were negative for both Mϕ and FPR2/ALX. In contrast, M1Mϕ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mϕ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mϕ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A4 (LXA4) production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E2. Stimulation with either mediator induced LXA4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this appears to be of insufficient duration and magnitude in natural tendon injury, which may potentiate chronic inflammation and fibrotic repair, as indicated by the presence of M2Mϕ.
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DOI：
10.1016/j.plefa.2005.05.008
发表时间：
2005-09-01
影响因子：
3
作者：
Gavins, FNE;Sawmynaden, P;Perretti, M
通讯作者：
Perretti, M
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
影响因子：
2.4
作者：
Herrmann-Hoesing, L. M.;Noh, S. M.;Knowles, D. P.
通讯作者：
Knowles, D. P.
影响因子：
2.8
作者：
Dahlgren, LA;van der Meulen, MCH;Nixon, AJ
通讯作者：
Nixon, AJ
影响因子：
11.8
作者：
Arur, S;Uche, UE;Han, DK
通讯作者：
Han, DK