title: The cationic peptide LL-37 binds Mac-1 (CD11b/CD18) with a low dissociation rate and promotes phagocytosis.
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 β2 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.
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Goran
authors.initials: G
authors.lastname: Bajic
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Gregers R
authors.initials: GR
authors.lastname: Andersen
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark.
authors.forename: Stig Hill
authors.initials: SH
authors.lastname: Christiansen
authors.affiliation: Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark; MEMBRANES Research Center, Aarhus University, DK-8000 Aarhus C, Denmark. Electronic address: vorup-jensen@biomed.au.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorup-Jensen
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018821:CD18 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis / Q000235:genetics; D011485:Protein Binding; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D018821:CD18 Antigens; D016177:Macrophage-1 Antigen; D054804:Cathelicidins
keywords: Cell adhesion, anti-microbial peptides; Ligand binding kinetics; Phagocytosis; von Willebrand Factor (vWF) Type A domain; β-2 (CD18) integrins