The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis

Xianwei Zhang, Goran Bajic, Gregers R Andersen, Stig Hill Christiansen, Thomas Vorup-Jensen

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Abstract

As a broad-spectrum anti-microbial peptide, LL-37 plays an important role in the innate immune system. A series of previous reports implicates LL-37 as an activator of various cell surface receptor-mediated functions, including chemotaxis in integrin CD11b/CD18 (Mac-1)-expressing cells. However, evidence is scarce concerning the direct binding of LL-37 to these receptors and investigations on the associated binding kinetics is lacking. Mac-1, a member of the β 2 integrin family, is mainly expressed in myeloid leukocytes. Its critical functions include phagocytosis of complement-opsonized pathogens. Here, we report on interactions of LL-37 and its fragment FK-13 with the ligand-binding domain of Mac-1, the α-chain I domain. LL-37 bound the I-domain with an affinity comparable to the complement fragment C3d, one of the strongest known ligands for Mac-1. In cell adhesion assays both LL-37 and FK-13 supported binding by Mac-1 expressing cells, however, with LL-37-coupled surfaces supporting stronger cell adhesion than FK-13. Likewise, in phagocytosis assays with primary human monocytes both LL-37 and FK-13 enhanced uptake of particles coupled with these ligands but with a tendency towards a stronger uptake by LL-37.

Original languageEnglish
JournalB B A - Proteins and Proteomics
Volume1864
Issue5
Pages (from-to)471-478
Number of pages8
ISSN1570-9639
DOIs
Publication statusPublished - 11 Feb 2016

Keywords

  • Cell adhesion, anti-microbial peptides
  • Ligand binding kinetics
  • Phagocytosis
  • von Willebrand Factor (vWF) Type A domain
  • β-2 (CD18) integrins

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