Accelerated healing of skin burns by anti-Gal/α-gal liposomes interaction

Abstract 

Topical application of α-gal liposomes on burns results in rapid local recruitment of neutrophils and macrophages. Recruited macrophages are pivotal for healing of burns because they secrete cytokines/growth factors that induce epidermis regeneration and tissue repair. α-Gal liposomes have glycolipids with α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting ∼1% of immunoglobulins. Interaction of α-gal liposomes with anti-Gal within the fluid film formed on burns, activates complement and generates chemotactic complement cleavage peptides which effectively recruit neutrophils and macrophages. Anti-Gal IgG coating α-gal liposomes further binds to Fcγ receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of α-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of α1,3galactosyltransferase knockout mice. These mice are the only available nonprimate mammals that can produce anti-Gal in titers similar to those in humans. Pairs of burns in mice were covered either with a spot bandage coated with 10mg α-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the α-gal liposomes treated burns contained ∼5-fold as many neutrophils as control burns, whereas macrophages were found only in α-gal liposomes treated burns. On Day 6, 50–100% of the surface area of α-gal liposomes treated burns were covered with regenerating epidermis (re-epithelialization), whereas almost no epidermis was found in control burns. The extensive recruitment of macrophages by anti-Gal/α-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing α-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with α-gal liposomes will be effective also in patients with burns and other skin wounds.

Abbreviations: α-gal epitope, Galα1-3Galβ1-4GlcNAc-R epitope, α1,3GT, α1,3galactosyltransferase, KO mice, knockout mice for the α1,3galactosyltransferase gene, α-gal liposomes, liposomes with glycolipids that carry α-gal epitopes, PKM, pig kidney membranes, PVA, polyvinyl alcohol

Keywords: Skin burn, Wound healing, α-Gal glycolipids, Anti-Gal antibody