000171228 001__ 171228
000171228 005__ 20260515163946.0
000171228 0247_ $$2doi$$a10.1021/acsami.6c04089
000171228 0248_ $$2sideral$$a149323
000171228 037__ $$aART-2026-149323
000171228 041__ $$aeng
000171228 100__ $$aPérez, Estela
000171228 245__ $$aMacrophage-Mediated In Vivo Intracellular Crystallization of Aluminum Oxyhydroxide Adjuvant in Vaccine-Induced Granulomas
000171228 260__ $$c2026
000171228 5060_ $$aAccess copy available to the general public$$fUnrestricted
000171228 5203_ $$aAluminum (Al) in the form of γ-aluminum oxyhydroxide (γ-AlOOH) nanoparticles has been used as a vaccine adjuvant for nearly a century. At injection sites, animals and humans develop granulomatous inflammation, in which macrophages may contain intracellular crystalline-like structures, so-called crystalloid bodies (CBs), morphologically distinct from the injected adjuvant. This raised the hypothesis that CBs may originate from the in vivo crystallization of γ-AlOOH within macrophages. To test this, six sheep received two subcutaneous doses of a γ-AlOOH-adjuvanted viral vaccine, while six controls received the same antigen without an adjuvant. All injection sites (AlOOH: n = 12; controls: n = 12) were examined by hematoxylin and eosin, modified aluminum hematoxylin, and lumogallion fluorescence. Al and CBs occurred exclusively in AlOOH-vaccinated tissues. The adjuvant stock and vaccine formulations were characterized ex situ using a combination of structural and imaging techniques. Four granulomas containing CBs, collected 133 days postinjection, were further examined using in situ imaging and crystallographic approaches. No crystalline structures resembling CBs were identified in the injected products; only γ-AlOOH nanoparticles were present. In post-mortem granulomas, macrophages contained Al-positive vacuoles filled with nanoparticle aggregates compatible with γ-AlOOH, often adjacent to CBs. Crystallographic analyses demonstrated that CBs were highly ordered γ-Al2O3 microcrystals, and advanced SEM-EDS with elemental mapping similarly distinguished γ-AlOOH nanoparticles and CBs as separate phases. These findings support an in vivo formation of γ-Al2O3 microcrystals from γ-AlOOH nanoparticles within macrophages under physiological conditions. To our knowledge, these findings provide evidence consistent with Al crystallization within mammalian cells and suggest that macrophage phagolysosomal conditions may represent a previously unrecognized biomimetic pathway for γ-Al2O3 formation. This finding may offer a biological model for the development of green and low-energy synthesis strategies for γ-Al2O3, with potential industrial applications as well as relevance to immunotoxicology, pathology, and cell
biology in the context of vaccine adjuvants.
000171228 536__ $$9info:eu-repo/grantAgreement/ES/MCIU/RTI2018-096172-B-C33$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-127847OB-I00$$9info:eu-repo/grantAgreement/ES/MICIU/CEX2023-001286-S$$9info:eu-repo/grantAgreement/ES/MICIU/PID2024–160339OB-I00
000171228 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000171228 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000171228 700__ $$0(orcid)0000-0001-7702-9619$$aNavarro, Marta$$uUniversidad de Zaragoza
000171228 700__ $$0(orcid)0000-0002-4599-3013$$aIbarra, Alfonso$$uUniversidad de Zaragoza
000171228 700__ $$0(orcid)0000-0002-1204-4356$$ade Blas, Ignacio$$uUniversidad de Zaragoza
000171228 700__ $$0(orcid)0000-0002-8133-2124$$aPérez, Marta$$uUniversidad de Zaragoza
000171228 700__ $$0(orcid)0000-0002-2053-9842$$aLuján, Lluís$$uUniversidad de Zaragoza
000171228 700__ $$0(orcid)0000-0002-6873-5244$$aSebastián, Víctor$$uUniversidad de Zaragoza
000171228 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal
000171228 7102_ $$11001$$2025$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Anatom.Anatom.Patológ.Com
000171228 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000171228 7102_ $$10$$2X$$aUniversidad de Zaragoza$$bInstitutos Univ. de Investig.$$cÁrea RPT Laboral INMA
000171228 773__ $$g18, 18 (2026), 25960-25978$$pACS appl. mater. interfaces$$tACS applied materials & interfaces$$x1944-8244
000171228 8564_ $$s5648009$$uhttps://zaguan.unizar.es/record/171228/files/texto_completo.pdf$$yVersión publicada
000171228 8564_ $$s3473746$$uhttps://zaguan.unizar.es/record/171228/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000171228 909CO $$ooai:zaguan.unizar.es:171228$$particulos$$pdriver
000171228 951__ $$a2026-05-15-14:55:30
000171228 980__ $$aARTICLE