Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis
García-Laorden, M. Isabel; Hoogendijk, Arie J.; Wiewel, Maryse A.; van Vught, Lonneke A.; Schultz, Marcus J.; Bovenschen, Niels; de Vos, Alex F.; van der Poll, Tom
(2021) Clinical and Experimental Immunology, volume 205, issue 2, pp. 222 - 231
(Article)
Abstract
Sepsis is a complex syndrome related to an infection-induced exaggerated inflammatory response, which is associated with a high mortality. Granzymes (Gzm) are proteases mainly found in cytotoxic lymphocytes that not only have a role in target cell death, but also as mediators of infection and inflammation. In this study we
... read more
sought to analyse the intracellular expression of GzmA, B, M and K by flow cytometry in diverse blood lymphocyte populations from 22 sepsis patients, 12 non-infected intensive care unit (ICU) patients and 32 healthy controls. Additionally, we measured GzmA and B plasma levels. Both groups of patients presented decreased percentage of natural killer (NK) cells expressing GzmA, B and M relative to healthy controls, while sepsis patients showed an increased proportion of CD8+ T cells expressing GzmB compared to controls. Expression of GzmK remained relatively unaltered between groups. Extracellular levels of GzmB were increased in non-infected ICU patients relative to sepsis patients and healthy controls. Our results show differential alterations in intracellular expression of Gzm in sepsis patients and non-infected critically ill patients compared to healthy individuals depending on the lymphocyte population and on the Gzm.
show less
Download/Full Text
Keywords: granzymes, infection, inflammation, sepsis, Sepsis/metabolism, CD8-Positive T-Lymphocytes/metabolism, Humans, Middle Aged, Critical Illness, Granzymes/metabolism, Male, Killer Cells, Natural/metabolism, Female, Lymphocyte Subsets/metabolism, Lymphocyte Count/methods, Immunology and Allergy, Immunology, Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't
ISSN: 0009-9104
Publisher: Wiley-Blackwell
Note: Funding Information: This study was partially supported by a Marie Curie Intra European Fellowship within the 7th Framework Programme – People (PIEF‐GA‐2011‐300895), and by the Center for Translational Molecular Medicine ( http://www.ctmm.nl ), project Molecular Diagnosis and Risk Stratification of Sepsis (grant no. 04I‐201). The funding agencies have no role in the design of the study, collection, analysis or interpretation of data, or in the writing of the manuscript. The authors are grateful to the patients and the healthy volunteers for their trust and cooperation. The authors also thank the Department of Immunopathology at Sanquin Research, especially to Gerard J. van Mierlo, for providing the GzmA and B ELISAs. Publisher Copyright: © 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology © 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.
(Peer reviewed)