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

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.

Modification of material surfaces with a ligand peptide for immune inhibitory receptor, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), significantly reduces the secretion of inflammatory cytokines of macrophages in response to proinflammatory stimuli. The LAIR-1 ligand peptide is derived from the extracellular matrix protein collagen, and the incorporation of this ligand peptide to biomaterial surfaces may be a strategy to suppress local inflammatory responses toward implanted materials.

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