Department of Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA.
J Immunol. 2011 Apr 1;186(7):4422-32. doi: 10.4049/jimmunol.1002324. Epub 2011 Feb 25.
Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galα1-3Galβ1-4GlcNAc-R epitopes (α-gal liposomes) on wounds may accelerate the healing process by rapid recruitment and activation of macrophages in wounds. Immune complexes of the natural anti-Gal Ab (constituting ∼1% of Ig in humans) bound to its ligand, the α-gal epitope on α-gal liposomes would induce local activation of complement and generation of complement chemotactic factors that rapidly recruit macrophages. Subsequent binding of the Fc portion of anti-Gal coating α-gal liposomes to FcγRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in α1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack α-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with α-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in α-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of α-gal liposomes resulted in their conversion into submicroscopic α-gal nanoparticles. These α-gal nanoparticles diffused more efficiently in wounds and further increased the efficacy of the treatment, resulting in 95-100% regeneration of the epidermis in wounds within 6 d. The study suggests that α-gal liposome and α-gal nanoparticle treatment may enhance wound healing in the clinic because of the presence of high complement activity and high anti-Gal Ab titers in humans.
巨噬细胞在促进伤口愈合中起着关键作用。我们假设在伤口上局部应用携带 Galα1-3Galβ1-4GlcNAc-R 表位（α-半乳糖脂）的脂质体可以通过快速募集和激活伤口中的巨噬细胞来加速愈合过程。天然抗 Gal Ab（构成人类 Ig 的约 1%）与 α-半乳糖脂上的 α-半乳糖表位形成的免疫复合物会诱导局部补体激活和产生补体趋化因子，从而迅速募集巨噬细胞。随后，抗 Gal 涂层 α-半乳糖脂的 Fc 部分与募集的巨噬细胞上的 FcγR 结合，可能激活编码介导伤口愈合的细胞因子的巨噬细胞基因。我们在 α1,3 半乳糖基转移酶敲除小鼠中记录了这种治疗的效果。与野生型小鼠相比，这些敲除小鼠缺乏 α-半乳糖表位，并且可以产生抗 Gal Ab。用 α-半乳糖脂处理的切除皮肤伤口的愈合时间是对照伤口的两倍。此外，α-半乳糖脂处理的伤口中的疤痕形成要低得多，接近生理性愈合。对 α-半乳糖脂进行额外的超声处理会导致其转化为亚微观的 α-半乳糖纳米颗粒。这些 α-半乳糖纳米颗粒在伤口中扩散得更有效，进一步提高了治疗效果，使伤口中的表皮在 6 天内 95-100%再生。该研究表明，由于人类中存在高补体活性和高抗 Gal Ab 滴度，α-半乳糖脂和 α-半乳糖纳米颗粒治疗可能会增强临床中的伤口愈合。
