title: In vitro activation of human macrophages by alginate-polylysine microcapsules.
abstract: Microencapsulated islets of Langerhans have been proposed as a bioartificial pancreas. However, foreign body reaction with fibrosis has been observed around implanted microcapsules. Since macrophages are present in this reaction and interleukin-1 (IL-1), a cytokine released by activated macrophages, may induce fibrosis, we tested the capacity of alginate-polylysine microcapsules to activate macrophages. Human monocytes were isolated from whole blood of healthy donors by a Ficoll density gradient and adherence to a plastic support. Monocytes were cultured for 24 h with: (1) alginate-polylysine microcapsules; (2) lipopolysaccharide (LPS) (positive control group); and (3) alone (negative control group). Monocyte activation was evaluated by measuring the secretion of IL-1 beta and the production of intracellular IL-1 alpha and IL-1 beta. Macrophages characterization was performed by immunocytological subtyping. IL-1 beta release and intracellular IL-1 beta and IL-1 alpha production were significantly higher when macrophages were cultured with alginate-polylysine microcapsules than when macrophages were cultured alone. In conclusion, macrophages are activated in vitro by alginate-polylysine microcapsules. This effect may be involved in the fibrosis observed in vivo around implanted microcapsules. In addition, interleukin-1, released during macrophage activation, may cross the microcapsule membrane and impair islet function.
authors.affiliation: INSERM U341, Service de Diabétologie, Hôtel-Dieu, Paris, France.
authors.forename: M E
authors.initials: ME
authors.lastname: Pueyo
authors.forename: S
authors.initials: S
authors.lastname: Darquy
authors.forename: F
authors.initials: F
authors.lastname: Capron
authors.forename: G
authors.initials: G
authors.lastname: Reach
mesh_terms: D000464:Alginates / Q000494:pharmacology* / Q000633:toxicity; D001672:Biocompatible Materials / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D004339:Drug Compounding; D005355:Fibrosis; D005549:Foreign-Body Reaction / Q000139:chemically induced; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008567:Membranes, Artificial; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011107:Polylysine / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008567:Membranes, Artificial; D011107:Polylysine; D020723:Glucuronic Acid