| First Author | Wigglesworth KM | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 7 | Pages | 4422-32 |
| PubMed ID | 21357545 | Mgi Jnum | J:170687 |
| Mgi Id | MGI:4947149 | Doi | 10.4049/jimmunol.1002324 |
| Citation | Wigglesworth KM, et al. (2011) Rapid Recruitment and Activation of Macrophages by Anti-Gal/{alpha}-Gal Liposome Interaction Accelerates Wound Healing. J Immunol 186(7):4422-32 |
| abstractText | Macrophages are pivotal in promoting wound healing. We hypothesized that topical application of liposomes with glycolipids that carry Galalpha1-3Galbeta1-4GlcNAc-R epitopes (alpha-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 approximately 1% of Ig in humans) bound to its ligand, the alpha-gal epitope on alpha-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 alpha-gal liposomes to FcgammaRs on recruited macrophages may activate macrophage genes encoding cytokines that mediate wound healing. We documented the efficacy of this treatment in alpha1,3galactosyltrasferase knockout mice. In contrast to wild-type mice, these knockout mice lack alpha-gal epitopes and can produce the anti-Gal Ab. The healing time of excisional skin wounds treated with alpha-gal liposomes in these mice is twice as fast as that of control wounds. Moreover, scar formation in alpha-gal liposome-treated wounds is much lower than in physiologic healing. Additional sonication of alpha-gal liposomes resulted in their conversion into submicroscopic alpha-gal nanoparticles. These alpha-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 alpha-gal liposome and alpha-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. |
