title: Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.
abstract: Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles.
authors.affiliation: Department of Biomedical Laboratory Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Ohlsson
authors.forename: Christopher
authors.initials: C
authors.lastname: Exley
authors.forename: Anna
authors.initials: A
authors.lastname: Darabi
authors.forename: Emma
authors.initials: E
authors.lastname: Sandén
authors.forename: Peter
authors.initials: P
authors.lastname: Siesjö
authors.forename: Håkan
authors.initials: H
authors.lastname: Eriksson
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology*; D056668:Cathepsin L / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053583:Interleukin-1beta / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010588:Phagosomes / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D000535:Aluminum; D056668:Cathepsin L
keywords: Aluminium adjuvant; Inflammasome; Mitochondria and phagolysosome; NLRP3