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A Study of Macrophages in the Aging Liver and in the Host Response to Engineered Lung Scaffolds
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | A Study of Macrophages in the Aging Liver and in the Host Response to Engineered Lung Scaffolds. |
| 개인저자 | Stahl, Elizabeth C. |
| 단체저자명 | University of Pittsburgh. School of Medicine. |
| 발행사항 | [S.l.]: University of Pittsburgh., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 170 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781085725026 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pittsburgh, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Brown, Bryan |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Macrophages are innate immune cells that contribute to tissue remodeling and homeostasis, respond to foreign antigens, and regulate the recruitment and activation of auxiliary immune cells. In chronic disease or a foreign body reaction, macrophages drive inflammation, leading to tissue damage and fibrosis. As such, understanding the developmental and phenotypical diversity of macrophages is of interest in both the pathobiology of disease as well as the design of novel therapeutics and materials. The dissertation examines macrophage biology in two contexts: the aging liver and the host response to engineered lung scaffolds.The liver contains two subsets of macrophages: a stable population of embryonically-derived Kupffer cells and a transient population of monocyte-derived macrophages. The dynamics of hepatic macrophages during the process of aging is unknown and may influence the development of chronic liver disease. Studies presented here demonstrate an increase in hepatic macrophages from naturally aged (19-months-old) mice compared to young counterparts (3-months-old). Macrophages from aged livers express significantly greater amounts of CD11b surface antigen and upregulate arginase strongly after exposure to interleukin-4, suggesting monocytic origins and a predisposition towards an alternatively activated phenotype. Aged livers also have increased triglycerides and pro-inflammatory signals, including monocyte chemoattractant protein (MCP-1). Inhibiting MCP-1 signaling reduced lipids and inflammation but did not significantly alter macrophage populations. Additional methods to modulate hepatic macrophages remain to be studied in the context of age-associated pathologies.Following the implantation of biomaterials, macrophages are recruited and polarize to a classical or alternatively activated phenotype, which can influence the outcome of the foreign body response. A positive response is associated with reduced inflammation and is crucial for the success of animal-derived organs to be used for xenotransplantation. Studies presented herein demonstrate that the removal of the foreign Gal-epitope from decellularized porcine lung scaffolds improves the host response in non-human primates, in part by reducing CD86 expression on macrophages and preventing substantial adaptive immune recognition upon reimplantation.Taken together, these studies further the understanding of macrophage biology in the aging liver and in the host response to Gal-epitopes and demonstrate novel strategies to reduce inflammation in chronic disease and tissue engineering contexts. |
| 일반주제명 | Pathology. Biomedical engineering. Immunology. |
| 언어 | 영어 |
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