Department of Pathology
Cellular and Molecular Physiology | Fluids and Secretions | Hemic and Immune Systems | Immunopathology | Immunoprophylaxis and Therapy | Pathological Conditions, Signs and Symptoms | Pathology
Transport of tissue-derived lymphatic fluid and clearance by draining lymph nodes are pivotal for maintenance of fluid homeostasis in the body and for immune-surveillance of the self- and non-self-proteomes. Yet a quantitative analysis of nodal filtration of the tissue-derived proteome present in lymphatic fluid has not been reported. Here we quantified the efficiency of nodal clearance of the composite proteomic load using label-free and isotope-labeling proteomic analysis of pre-nodal and post-nodal samples collected by direct cannulation. These results were extended by quantitation of the filtration efficiency of fluorophore-labeled proteins, bacteria, and beads infused at physiological flow rates into pre-nodal lymphatic collectors and collected by post-nodal cannulation. We developed a linear model of nodal filtration efficiency dependent on pre-nodal protein concentrations and molecular weight, and uncovered criteria for disposing the proteome incoming from defined anatomical districts under physiological conditions. These findings are pivotal to understanding the maximal antigenic load sustainable by a draining node, and promote understanding of pathogen spreading and nodal filtration of tumor metastasis, potentially helping to improve design of vaccination protocols, immunization strategies and drug delivery.
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© The Author(s) 2018. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
Sci Rep. 2018 Jul 26;8(1):11253. doi: 10.1038/s41598-018-29614-0. Link to article on publisher's site
Clement, Cristina C.; Wang, Wei; Dzieciatkowska, Monika; Cortese, Marco; Hansen, Kirk C.; Becerra, Aniuska; Thangaswamy, Sangeetha; Nizamutdinova, Irina; Moon, Jee-Young; Stern, Lawrence J.; Gashev, Anatoliy A.; Zawieja, David; and Santambrogio, Laura, "Quantitative Profiling of the Lymph Node Clearance Capacity" (2018). Open Access Articles. 3535.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Cellular and Molecular Physiology Commons, Fluids and Secretions Commons, Hemic and Immune Systems Commons, Immunopathology Commons, Immunoprophylaxis and Therapy Commons, Pathological Conditions, Signs and Symptoms Commons, Pathology Commons