Worcester, Mass. From the Department of Surgery, University of Massachusetts Medical School.
Plast Reconstr Surg. 2012 Feb;129(2):242e-251e. doi: 10.1097/PRS.0b013e31823aebb1.
The α-gal epitope is a carbohydrate antigen that interacts specifically with the natural anti-Gal antibody--the most abundant antibody in humans. Anti-Gal/α-gal epitope interaction activates complement to generate chemotactic factors that induce rapid recruitment of macrophages. The authors hypothesized that α-gal epitopes on nanoparticles can accelerate wound healing by inducing rapid recruitment and activation of macrophages in wounds.
α-Gal nanoparticles were generated from phospholipids, cholesterol, and α-gal glycolipids. α-Gal nanoparticle treatment of wounds was studied in 12 α1,3galactosyltrasferase knockout pigs. Like humans, these pigs lack α-gal epitopes and produce the natural anti-Gal antibody. Full-thickness wounds (20 × 20 mm) with tattooed borders were created on the back of pigs. α-Gal nanoparticles (10 or 100 mg) were topically applied onto the wounds. Saline-treated wounds served as control. Wound open surface area was measured every 3 to 4 days during dressing changes. Wounds from euthanized pigs were subjected to histological evaluation.
Treated wounds displayed many more macrophages and increased angiogenesis than control wounds in the same pig. On day 10, wounds treated with 10 mg and 100 mg displayed 35 and 60 percent decreased open surface area compared with control wounds, respectively, and 80 and 90 percent less than control wounds on day 13 (p < 0.05). No keloid formation or no increase in scar formation was observed on day 60.
α-Gal nanoparticle treatment of wounds accelerates macrophage recruitment, angiogenesis, and wound healing in pigs producing the anti-Gal antibody. As humans produce high titers of anti-Gal antibodies, this treatment may exhibit a similar beneficial effect in the clinical setting.
α-半乳糖苷(α-gal)表位是一种碳水化合物抗原,与天然抗-α-半乳糖抗体(人类中最丰富的抗体)特异性结合。抗-α-gal/α-gal 表位相互作用激活补体,生成趋化因子,从而快速募集巨噬细胞。作者假设纳米颗粒上的 α-gal 表位可以通过在伤口中快速募集和激活巨噬细胞来加速伤口愈合。
从磷脂、胆固醇和 α-gal 糖脂生成 α-gal 纳米颗粒。作者在 12 只缺乏 α1,3-半乳糖基转移酶的基因敲除猪中研究了 α-gal 纳米颗粒对伤口的治疗作用。与人类一样,这些猪缺乏 α-gal 表位,且产生天然抗-α-gal 抗体。在猪背部制造全层(20×20mm)伤口,并带有纹身边界。将 α-gal 纳米颗粒(10 或 100mg)局部应用于伤口。盐水处理的伤口作为对照。在每次换药时测量 3 到 4 天的伤口开放表面积。处死猪后,对伤口进行组织学评估。
与同一猪的对照伤口相比,经处理的伤口显示出更多的巨噬细胞和增加的血管生成。在第 10 天,用 10mg 和 100mg 处理的伤口与对照伤口相比,分别显示出 35%和 60%的开放表面积减少,在第 13 天减少了 80%和 90%(p<0.05)。在第 60 天未观察到瘢痕疙瘩形成或瘢痕形成增加。
在产生抗-α-gal 抗体的猪中,α-gal 纳米颗粒处理伤口可加速巨噬细胞募集、血管生成和伤口愈合。由于人类产生高滴度的抗-α-gal 抗体,因此这种治疗在临床环境中可能具有类似的有益效果。