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New Study on Alumunium Adjuvants by Shardlow, Mold, Exley

AluminumThe Journal of Inorganic Biochemistry
12 November, 2019

The interaction of aluminium-based adjuvants with THP-1 macrophages in vitro: Implications for cellular survival and systemic translocation.

Emma Shardlow, Matthew Mold, Christopher Exley

Highlights

•Untreated THP-1 macrophages can survive for up to 9 days in vitro.
•After 9 days most cells have de-differentiated to a monocytic phenotype.
•Cells rapidly engulf aluminium particulates as early as 3 h post exposure.
•Most cells are not adversely impacted by intracellular aluminium adjuvant particles.

Abstract

Within clinical vaccinations, recombinant antigens are routinely entrapped inside or adsorbed onto the surface of aluminium salts in order to increase their immunological potency in vivo. The efficacy of these immunisations is highly dependent upon the recognition and uptake of these complexes by professional phagocytes and their subsequent delivery to the draining lymph nodes for further immunological processing. While monocytes have been shown to internalise aluminium adjuvants and their adsorbates, the role of macrophages in this respect has not been fully established. Furthermore, this study explored the interaction of THP-1 macrophages with aluminium-based adjuvants (ABAs) and how this relationship influenced the survival of such cells in vitro. THP-1 macrophages were exposed to low concentrations of ABAs (1.7 μg/mL Al) for a maximum of seven days. ABA uptake was determined using lumogallion staining and cell viability by both DAPI (4′,6-diamidino-2-phenylindole) staining and LDH (lactate dehydrogenase) assay. Evidence of ABA particle loading was identified within cells at early junctures following treatment and appeared to be quite prolific (>90% cells positive for Al signal after 24 h). Total sample viability (% LDH release) in treated samples was predominantly similar to untreated cells and low levels of cellular death were consistently observed in populations positive for Al uptake. It can thus be concluded that aluminium salts can persist for some time within the intracellular environment of these cells without adversely affecting their viability. These results imply that macrophages may play a role in the systemic translocation of ABAs once administered in the form of an inoculation.  Read more at Science Direct here.

Comments

David L

Monocyte-derived THP-1 macrophages internalize aluminum based adjuvants (ABAs) - cells rapidly engulf aluminum particulates as early as 3 hours post exposure. Evidence of ABA particle loading was identified within cells at early junctures following treatment and appeared to be quite prolific, with greater than 90% of cells positive for Al signal after 24 hours. These cells are then capable of disseminating their cargo throughout the body to myriad locations including the spleen, lymphatic nodes and brain. The extent or likelihood for systemic translocation is expected to be governed by the ability of aluminum loaded macrophages to survive for extended periods of time post uptake. This study is the first direct demonstration that the cellular internalization of ABAs by macrophages does not necessarily induce significant levels of cytotoxicity (being toxic to cells) and as a result, the majority of macrophages remained viable for up to 7 days after treatment while containing aluminum particulates. While such trends also need to be confirmed using primary MDMs, the longevity of these cells after engulfing aluminum particulates indirectly supports their role in cell-mediated particulate trafficking to the draining lymph nodes, which reportedly initially peaks around 4–7 days after vaccination. Clarification of the precise mechanisms through which ABAs perpetuate the survival of immunocompetent cells is required in order to better understand the risks associated with their biological administration in predisposed individuals, including the slow CCL2-dependent further dissemination of aluminum particles to the brain.

This study further supports that the injected aluminum specifically is contributing toward the aluminum accumulation in tissues and brain in some people via Monocyte-derived THP-1 macrophages rather than being dismissed as less relevant to potential harm compared to other aluminum we are exposed to via other routes. Aluminum has been found in inflammatory cells in the autism brains, alongside clear evidence of inflammatory cells heavily loaded with aluminium entering the brain via the surrounding membranes and those that separate the brain from circulating blood.

Monocyte chemoattractant protein-1 (MCP1) also known as CCL2 is a chemokine that is transiently and significantly up-regulated during inflammation and is able to disrupt the integrity of blood brain barrier and modulate the progression of various diseases. MCP1 is a pro-inflammatory mediator, whose up-regulation is found in many central nervous system disorders with blood brain barrier (BBB) breakdown. Granulomas which trap the Al adjuvant at the injection site initially occur after about 1% of vaccinations. The risk increases with the number of vaccines given. https://link.springer.com/article/10.1007/s00431-014-2318-2 However, most children with itching granulomas become contact allergic to aluminum.

Benedetta

Well, I guess we may have already known this; but science is all about repeated studies and seeing if they get the same results.

Soooooo, it looks like that is the case. More proof. More proof to the --- arrogant, selfish, all for themselves members of those IACC meetings. A doctor Pan and even a doctor's degree was not enough for him. That Tom Insel; some one that was gifted as he, since he was just a teenager knew he was going to do big things. Must be nice to know you will never starve, and die homeless cause you got a brain. Why did God them if they have ordinary survival skills of just here to go along and get along. What a waste.

Pft

The take home I guess is that the aluminum does not remain localized at the injection site but that immune cells like macrophages can transport it elsewhere via the lymphatic system which then drains to the circulatory system and and onwards to other areas like the brain if able to cross the blood brain barrier. I thought we already knew that , although I guess its not universally accepted

Benedetta

So, the macrophages don't die with smaller amounts of aluminum, and after seven or so days the leak themselves into the lymphatic system.

In some people like my daughter it leaks into the spleen and every small blood vessel in her body like Kawasaki's, there is plenty of lymphatic tissue in the spleen. Gherdari says it goes from there to the tonsils and then to the brain.

Or into the lymphatic tissue of the pancreas, like my grandnephew and cause diabetes, but all the while the doctors say he ran into some virus.

Smaller amounts the longer they live, and carry stuff around? Is this what this study is about? The smaller the amount the less cell death of some kind of immune cell?


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