Aging‐related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance

Aging Cell

Valerio Zolla¹  Irina Tsoy Nizamutdinova⁵  Brian Scharf¹  Cristina C. Clement¹  Daisuke Maejima⁵  Tony Akl⁶  Takashi Nagai⁵  Paola Luciani⁴  Jean-Christophe Leroux⁴  Cornelia Halin⁴  Sabriya Stukes³  Sangeeta Tiwari³  Arturo Casadevall³  William R. Jacobs Jr³  David Entenberg²  David C. Zawieja⁵  John Condeelis²  David R. Fooksman¹  Anatoliy A. Gashev⁵ 

[1] Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY, USA;Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA;Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland;Department of Medical Physiology, College of Medicine, Texas A&M University Health Science Center, Temple, TX, USA;Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA

关键词: aging;    mass spectrometry;    oxidative stress;    proteomics;    lymphatics;   

DOI  :  10.1111/acel.12330

来源: Wiley

【 摘 要 】

Summary

The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport.

【 授权许可】

CC BY   
© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.