Intracellular expression of granzymes A, B, K and M in blood lymphocyte subsets of critically ill patients with or without sepsis

M. Isabel García-Laorden, Arie J. Hoogendijk, Maryse A. Wiewel, Lonneke A. van Vught, Marcus J. Schultz, Niels Bovenschen, Alex F. de Vos, Tom van der Poll

Research output: Contribution to journalArticleAcademicpeer-review

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 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.
Original languageEnglish
Pages (from-to)222-231
Number of pages10
JournalClinical and experimental immunology
Volume205
Issue number2
Early online date2021
DOIs
Publication statusPublished - Aug 2021

Keywords

  • granzymes
  • infection
  • inflammation
  • sepsis

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