title: Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses.
abstract: Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this process. We first demonstrate that ASC(-/-) mice subjected to PMMA bead injections had reduced cell infiltration and altered collagen deposition, suggesting a role for the inflammasome in the FBR. We next investigated the NLRP3 and AIM2 sensors because of their known contributions in recognising damaged and apoptotic cells. We found that NLRP3 was dispensable for the fibrotic encapsulation; however AIM2 expression influenced leukocyte infiltration and controlled collagen deposition, suggesting a previously unexplored link between AIM2 and biomaterial-induced FBR.
authors: Experimental Therapeutics Laboratory, Sansom Institute and Hanson Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, 5000, Australia.
authors: Susan N
authors: SN
authors: Christo
authors: Experimental Therapeutics Laboratory, Sansom Institute and Hanson Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, 5000, Australia.|Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia.
authors: Kerrilyn R
authors: KR
authors: Diener
authors: Centre for Neurological Diseases, SA Pathology, Adelaide, SA 5000, Australia.
authors: Jim
authors: J
authors: Manavis
authors: Centre for Cancer Biology, University of South Australia and SA Pathology, SA 5000, Australia.
authors: Michele A
authors: MA
authors: Grimbaldeston
authors: Mawson Institute, University of South Australia, Adelaide, SA 5095, Australia.
authors: Akash
authors: A
authors: Bachhuka
authors: Mawson Institute, University of South Australia, Adelaide, SA 5095, Australia.
authors: Krasimir
authors: K
authors: Vasilev
authors: Experimental Therapeutics Laboratory, Sansom Institute and Hanson Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, 5000, Australia.|Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, 5005, Australia.|School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia.
authors: John D
authors: JD
authors: Hayball
mesh_terms: D000208:Acute Disease; D000327:Adsorption; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005547:Foreign Bodies / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007113:Immunity, Innate / Q000187:drug effects*; D016130:Immunophenotyping; D058847:Inflammasomes / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010533:Peritoneal Lavage; D019904:Polymethyl Methacrylate / Q000737:chemistry / Q000494:pharmacology; D019736:Prostheses and Implants
chemical_list: C540422:Aim2 protein, mouse; D051017:Apoptosis Regulatory Proteins; D001672:Biocompatible Materials; D001798:Blood Proteins; D053468:CARD Signaling Adaptor Proteins; D024042:Collagen Type I; D024043:Collagen Type II; D016207:Cytokines; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D019904:Polymethyl Methacrylate