title: Altered adherent leukocyte profile on biomaterials in Toll-like receptor 4 deficient mice.
abstract: The host response to a biomaterial is characterized by both acute recruitment and attachment of cells as well as chronic encapsulating tissue reaction. The implantation procedure induces production of damage-associated molecular patterns (DAMPs) which may contribute to host recognition of the material. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that bind not only pathogen-associated molecular patterns (PAMPs) but also DAMPs. We sought to investigate whether TLR4/DAMP interactions were involved in the acute and chronic inflammatory response to an implanted biomaterial. When PET discs were implanted intraperitoneally for 16h, no differences were found in the number of leukocytes recruited between TLR4(+) (C57BL/10J) and TLR4(-) (C57BL/10ScNJ) mice. However, a significant shift in the leukocyte profile on the biomaterial surface was observed for TLR4(-) mice. While the total number of adherent cells was the same in both strains, TLR4(+) mice had a profile with equivalent neutrophil and monocyte/macrophage presence on the material surface, and TLR4(-) mice had a profile of predominantly neutrophils with fewer monocyte/macrophages. When implants were placed subcutaneously for 2 weeks, the fibrous capsule thicknesses were not different between TLR4(+) and TLR4(-) mouse strains. These findings illustrate that TLR4 may play a role in the initial recognition of a biomaterial by directing the adhesive cellular profile.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
authors.forename: Todd H
authors.initials: TH
authors.lastname: Rogers
authors.forename: Julia E
authors.initials: JE
authors.lastname: Babensee
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009132:Muscles / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D012867:Skin / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha