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The interaction between polarized macrophages and fibroblasts in giant cell arteritis

Walinga, Fokke (2022) The interaction between polarized macrophages and fibroblasts in giant cell arteritis. Master's Research Project 1, Biomedical Sciences.

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Abstract

Giant cell arteritis (GCA) is the most frequent form of vasculitis in older individuals mainly affecting the aorta and extracranial branches of the carotid artery. Vascular lesions are mainly dictated by polarized macrophages (MØs) that are responsible for persistent inflammation, media and elastic lamina degradation, neo-angiogenesis, and intima hyperplasia. Recently, two spatially distributed MØ subsets were discovered associated with tissue destruction and remodeling in GCA lesions. It was proposed that local production of granulocyte macrophage colony-stimulating factor (GM-CSF) skews media resident MØs into CD206+, YKL-40+, and IL-6high MØs (GM-MØs), which sequentially prime surrounding MØs with monocyte colony-stimulating factor into FR-b+ and PDGF-AAhigh MØs (M-MØs) located at the adventitia and intima. It is hypothesized that YKL-40 and PDGF-AA are important players in the interaction between GM/M-MØs and fibroblasts in GCA lesions regarding fibroblast proliferation and migration. This crosstalk between GM/M-MØs and fibroblasts can potentially be exploited for GCA-specific markers for diagnosis and treatment. To study this crosstalk, healthy control monocytes were in vitro differentiated in the presence of GM/M-CSF into GM/M-MØs and subsequently stimulated with LPS. MØ culture supernatants were acquired and added to cultures of healthy control fibroblasts to study proliferation (MTT assay) and migration (scratch assay). ELISA and qPCR showed no overexpression of...

Item Type: Thesis (Master's Research Project 1)
Supervisor name: Jiemy, W.F. and Heeringa, P.
Degree programme: Biomedical Sciences
Thesis type: Master's Research Project 1
Language: English
Date Deposited: 22 Jun 2022 13:02
Last Modified: 22 Jun 2022 13:02
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/27354

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