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Histological Quantification to Determine Lung Fungal Burden in Experimental Aspergillosis
Published on: March 9, 2018
Interactions of Aspergillus fumigatus with vascular endothelial cells
Y Kamai1, L Y Chiang, L M Lopes Bezerra
1Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Abstract:
Invasive aspergillosis is characterized by two different types of angioinvasion. During pulmonary aspergillosis, hyphae are initially outside of the pulmonary vasculature and they invade the endothelial cell lining of the blood vessels by passing from the abluminal to the luminal surface. Some of these hyphal fragments can break off and circulate in the bloodstream. In severely immunocompromised hosts, these blood-borne hyphal fragments adhere to the luminal surface of the endothelial cells and they penetrate the endothelial cell lining of the vasculature by passing from the luminal to the abluminal surface. We have set up in vitro models of luminal and abluminal endothelial cell invasion by Aspergillus fumigatus. Luminal invasion by hyphae results in both endothelial cell damage and stimulation of tissue factor expression. Abluminal invasion causes less endothelial cell damage than luminal invasion, but greater induction of endothelial cells genes encoding cytokines, leukocyte adhesion molecules and tissue factor. These differences in the endothelial cell response to luminal versus abluminal infection may indicate significant differences in the pathogenesis of hematogenously disseminated versus locally invasive versus aspergillosis.
Insights
Invasive aspergillosis involves two angioinvasion types. Aspergillus fumigatus hyphae invade endothelial cells from outside (abluminal) or inside (luminal), impacting disease progression differently.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Invasive aspergillosis presents distinct angioinvasion patterns.
- Pulmonary aspergillosis involves abluminal invasion of vasculature by hyphae.
- Disseminated disease involves blood-borne hyphal fragments invading from the lumen.
Purpose of the Study:
- To establish in vitro models simulating luminal and abluminal endothelial cell invasion by Aspergillus fumigatus.
- To compare the cellular responses to these two distinct invasion pathways.
Main Methods:
- Development of in vitro models for Aspergillus fumigatus luminal and abluminal endothelial cell invasion.
- Assessment of endothelial cell damage and gene expression (cytokines, adhesion molecules, tissue factor) following invasion.
Main Results:
- Luminal invasion by Aspergillus fumigatus caused significant endothelial cell damage and stimulated tissue factor expression.
- Abluminal invasion resulted in less endothelial cell damage but greater induction of genes for cytokines, leukocyte adhesion molecules, and tissue factor.
Conclusions:
- Distinct endothelial cell responses to luminal versus abluminal Aspergillus fumigatus invasion suggest different pathogenic mechanisms.
- Findings may elucidate differences in the pathogenesis of locally invasive, hematogenously disseminated aspergillosis.
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