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

Uri Galili, Kim Wigglesworth, Ussama M. Abdel-Motal

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 10 mg 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.

Original languageEnglish
Pages (from-to)239-251
Number of pages13
JournalBurns
Volume36
Issue number2
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Fingerprint

Burns
Liposomes
Skin
Macrophages
Epidermis
Bandages
Intercellular Signaling Peptides and Proteins
Neutrophils
Re-Epithelialization
Cytokines
Polyvinyl Alcohol
Fc Receptors
Neutrophil Infiltration
Glycolipids
Knockout Mice
Immunoglobulins
Epitopes
Regeneration
Mammals
Theoretical Models

Keywords

  • α-Gal glycolipids
  • Anti-Gal antibody
  • Skin burn
  • Wound healing

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Emergency Medicine
  • Surgery

Cite this

Accelerated healing of skin burns by anti-Gal/α-gal liposomes interaction. / Galili, Uri; Wigglesworth, Kim; Abdel-Motal, Ussama M.

In: Burns, Vol. 36, No. 2, 03.2010, p. 239-251.

Research output: Contribution to journalArticle

Galili, Uri ; Wigglesworth, Kim ; Abdel-Motal, Ussama M. / Accelerated healing of skin burns by anti-Gal/α-gal liposomes interaction. In: Burns. 2010 ; Vol. 36, No. 2. pp. 239-251.
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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 10 mg 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.",
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