Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR-1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses

Adv Healthc Mater. 2017 Dec;6(24):10.1002/adhm.201700707. doi: 10.1002/adhm.201700707. Epub 2017 Oct 30.

Abstract

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory receptor broadly expressed on immune cells, with its ligands residing within the extracellular matrix protein collagen. In this study, surfaces are modified with a LAIR-1 ligand peptide (LP), and it is observed that macrophages cultured on LAIR-1 LP-conjugated surfaces exhibit significantly reduced secretion of inflammatory cytokines in response to proinflammatory stimuli that reflect an injured environment. These downregulated mediators include TNF-α, MIP-1α, MIP-1β, MIP-2, RANTES, and MIG. Knockdown of LAIR-1 using siRNA abrogates this inhibition of cytokine secretion, supporting the specificity of the inhibitory effect to this receptor. These results are the first to demonstrate that integration of LAIR-1 ligands with biomaterials could suppress inflammatory responses.

Keywords: LAIR-1; collagen peptides; immunomodulatory biomaterials; inflammation; macrophages.

MeSH terms

  • Biocompatible Materials / chemistry*
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Chemokine CCL4 / genetics
  • Chemokine CCL4 / metabolism
  • Chemokine CCL5 / genetics
  • Chemokine CCL5 / metabolism
  • Chemokine CXCL2 / genetics
  • Chemokine CXCL2 / metabolism
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / metabolism
  • Gene Expression Regulation
  • Humans
  • Ligands
  • Macrophages / metabolism*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Protein Binding
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / metabolism*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biocompatible Materials
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL2
  • Chemokine CXCL9
  • Ligands
  • Peptides
  • Receptors, Immunologic
  • Tumor Necrosis Factor-alpha
  • leukocyte-associated immunoglobulin-like receptor 1