4.7 Article

Amyloid Beta Peptides Lead to Mast Cell Activation in a Novel 3D Hydrogel Model

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MDPI
DOI: 10.3390/ijms241512002

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Amyloid beta; Alzheimer's disease; brain; IgE; IL-33; neuroinflammation; mast cells; three-dimensional culture

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Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by the aggregation of toxic amyloid-beta (Aβ) and neuroinflammation. Mast cells (MCs), an innate immune cell type, play a role in the immune response in AD. A 3D culture system using collagen gel was developed to investigate the activation of MCs by Aβ peptides. The study found that MCs responded to Aβ deposition by secreting inflammatory mediators, with Aβ1-42 inducing the highest level of activation. This study demonstrates the importance of understanding neuroinflammation in AD through investigating MCs in a 3D environment.
Alzheimer's disease (AD) is a prevalent neurodegenerative disease and the world's primary cause of dementia among the elderly population. The aggregation of toxic amyloid-beta (A & beta;) is one of the main pathological hallmarks of the AD brain. Recently, neuroinflammation has been recognized as one of the major features of AD, which involves a network of interactions between immune cells. The mast cell (MC) is an innate immune cell type known to serve as a first responder to pathological changes and crosstalk with microglia and neurons. Although an increased number of mast cells were found near the sites of A & beta; deposition, how mast cells are activated in AD is not clear. We developed a 3D culture system to culture MCs and investigated the activation of MCs by A & beta; peptides. Because collagen I is the major component of extracellular matrix (ECM) in the brain, we encapsulated human LADR MCs in gels formed by collagen I. We found that 3D-cultured MCs survived and proliferated at the same level as MCs in suspension. Additionally, they can be induced to secrete inflammatory cytokines as well as MC proteases tryptase and chymase by typical MC activators interleukin 33 (IL-33) and IgE/anti-IgE. Culturing with peptides A & beta;1-42, A & beta;1-40, and A & beta;25-35 caused MCs to secrete inflammatory mediators, with A & beta;1-42 inducing the maximum level of activation. These data indicate that MCs respond to amyloid deposition to elicit inflammatory responses and demonstrate the validity of collagen gel as a model system to investigate MCs in a 3D environment to understand neuroinflammation in AD.

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