RESEARCH ARTICLE


Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity



Ravi Danielsson1, Andreas Svensson2, Peter Falkman1, Håkan Eriksson1, *
1 Department of Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden
2 Lund Stem Cell Center, BMC B10, Lund University, Lund, Sweden

Article Information


Identifiers and Pagination:

Year: 2018
Volume: 08
First Page: 1
Last Page: 15
Publisher Id: TOIJ-8-1
DOI: 10.2174/1874226201808010001

Article History:

Received Date: 03/11/2017
Revision Received Date: 24/02/2018
Acceptance Date: 08/03/2018
Electronic publication date: 30/03/2018
Collection year: 2018

© 2018 Danielsson et al .

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Biomedical Science, Faculty of Health and Society, Malmö University, Håkan Eriksson, SE-205 06 Malmö, Sweden; Tel: +46406657925; E-mail: hakan.eriksson@mah.se


Abstract

Background:

Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis.

Objective:

To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis.

Methods:

Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan.

Results:

No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4)y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4)y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan.

Conclusion:

Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity.

Keywords: Aluminium based adjuvant, Lumogallion, Mitochondrial activity, MTT assay, Phagocytosis, ABAS, Zeolites.