Activation of Human Monocytes by Colloidal Aluminum Salts

Abstract

Subunit vaccines often contain colloidal aluminum saltebased adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates. It is well-known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø ¼ 210 ± 40 nm) and rod-shaped boehmite (ø ¼ 83 ± 827 nm) was compared with classical aluminum oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite, or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation, and cytokine secretion, as measured by flow cytometry and enzyme-linked immunosorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the 7 surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate.

Aluminum Hydroxide And Aluminum Phosphate Adjuvants Elicit A Different Innate Immune Response

“…With respect to charge, Al(OH) 3 is positively charged at a physiological pH, even though this charge may be partly shielded by proteins and salts in the culture medium. 28 This positive charge of Al(OH) 3 allows for stronger interactions with the negatively charged cell membrane, compared to the slightly negatively charged AlPO 4 . 29 With respect to size, Al(OH) 3 particles are expected to have a more suitable size (i.e.…”

New developments in hair research

“…Bak and colleagues show that Boehmite has potential for promoting hair growth through inducing cell signalling and activation of anagen . Boehmite is an aluminium oxide hydroxide with a number of industrial purposes that is currently being investigated as a vaccine adjuvant . Perhaps, it may yet find a new role via its apparent cell growth and inflammatory modulating properties .…”

Aluminiodun txerto-laguntzaileen eraginaren azterketa sistemen biologiaren bidez

“…Zitokinen jariaketa ere aurkitu da, eta horiek erantzun immunea Th1 edo Th2 motara bideratu dezakete. Esperimentuen artean aurkitzen diren desberdintasunak aluminio-gatzen partikulen forma eta tamainarekin erlazionatuta egon daitezke, deskribatuta baitago ezaugarri horiek aluminio-laguntzaileen garraioan eta internalizazioan eragina dutela [31,39,40]. Ematen du laguntzaile horiek askotariko bideen bitartez lan egiten dutela; hau da, ez dago mekanismo bakar bat zeinaren bidez sistema immunea pizten ahal duten.…”