Farklı Tipteki Aluminyum Adjuvanların Monositik Hücrelerde Oluşturduğu Etkilerin Proteomiks ve Metabolomiks Düzeyde İncelenmesi
Özet
Kabakoğlu, F., Investigation of The Effects of Aluminium Adjuvants on
Monocytic Cells at The Proteomics and Metabolomics Level. Hacettepe
University, Hacettepe University Health Sciences Institute, Vaccine Studies
Program, Master Thesis, Ankara, 2023. Vaccines are biological compounds that
reduce the mortality and morbidity of diseases caused by infectious diseases by
mimicking natural infection and producing long-term immunological memory. Since
most of the antigens used in vaccines cause weak immunological response, adjuvants
are also added to the vaccine components in order to increase the potency and duration
of the effect of the vaccines. Since ancient times, aluminum salts have been the most
commonly used adjuvants and provide a particularly strong stimulus to monocytes to
differentiate into a mature dendritic phenotype. In this thesis, metabolomics and
proteomics studies were carried out using different concentrations of aluminum
oxyhydroxide (AH) and aluminum hydroxyphosphate (AP) salts in U-937 and THP-1
cell cultures. For this purpose, intracellular and extracellular metabolomics analyzes
with gas chromatography-mass spectrometry (GC-MS) and proteomics analyzes were
performed with liquid chromatography-cyclopol time-of-flight mass spectrometry
(LC-qTOF-MS). As a result of the analysis, a total of 170 metabolites and 403 proteins
were identified. Univariate and multivariate data analyzes allowed the identification
of metabolites, proteins and pathways that vary depending on aluminum adjuvant salts
and THP-1 and U937 cell culture types. It is thought that endogenic metabolites and
proteins that change significantly in cells exposed to different concentrations of AH
and AP salts may lead to the strengthening of the effect of existing aluminum adjuvants
and the development of new endogenous adjuvants.
