Accelerated healing of skin burns by anti-Gal/alpha-gal liposomes interaction.
Topical application of alpha-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. alpha-Gal liposomes have glycolipids with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting approximately 1% of immunoglobulins. Interaction of alpha-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 alpha-gal liposomes further binds to Fcgamma receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of alpha-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of alpha1,3galactosyltransferase 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 alpha-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the alpha-gal liposomes treated burns contained approximately 5-fold as many neutrophils as control burns, whereas macrophages were found only in alpha-gal liposomes treated burns. On Day 6, 50-100% of the surface area of alpha-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/alpha-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing alpha-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with alpha-gal liposomes will be effective also in patients with burns and other skin wounds.
Galili
Uri
U
Department of Surgery, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. Uri.Galili@umassmed.edu
Wigglesworth
Kim
K
Abdel-Motal
Ussama M
UM
D000818:Animals; D000937:Antigen-Antibody Reactions; D001458:Bandages; D002056:Burns / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002633:Chemotaxis; D004817:Epidermis / Q000502:physiology; D005700:Galactosyltransferases / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000276:immunology; D008081:Liposomes; D008264:Macrophages / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000473:pathology; D011817:Rabbits; D012038:Regeneration; D014312:Trisaccharides / Q000008:administration & dosage / Q000276:immunology*; D014945:Wound Healing
D007074:Immunoglobulin G; D008081:Liposomes; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D005700:Galactosyltransferases; C487611:alpha 1,3 galactosyltransferase, mouse