Tag Archives: neutrophils
Neutrophil activation at high-fat high-cholesterol and high-fructose diets induces low-grade inflammation in mice
G. Bila1, O. Vishchur2, V. Vovk3, S. Vari4, R. Bilyy1*
1Department of Histology, Cytology and Embryology,
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
2Institute of Animal Biology NAAS, Lviv, Ukraine;
3Department of Pathological Anatomy and Forensic Medicine,
Danylo Halytsky Lviv National Medical University, Lviv, Ukraine;
4International Research and Innovation in Medicine Program,
Cedars-Sinai Medical Center, Los Angeles, California, USA;
*e-mail: r.bilyy@gmail.com
Received: 05 February 2024; Revised: 17 March 2024;
Accepted: 17 March 2024; Available on-line: 30 April 2024
Nonalcoholic fatty liver disease (NAFLD), which can progress to nonalcoholic steatohepatitis (NASH), is a significant health concern affecting a substantial portion of the population. This study investigates the role of neutrophil extracellular traps (NETs) in liver inflammation induced by high-fat high-cholesterol diet (HFHCD) and high-fructose diet (HFD). The chronic nature of NAFLD involves low-grade inflammation with cytokine elevation. The research aims to visualize neutrophil elastase (NE) activity during HFHCD and HFD representing conditions of low-grade activation and assess neutrophil functional status. The study employs a mouse model subjecting animals to HFHCD, HFD or a standard diet (SD) for six weeks. Various analyses were used including histological evaluations, in vivo imaging of NE activity using a fluorescent probe, fluorescent microscopy, flow cytometry and assessment of neutrophil function through reactive oxygen species (ROS) levels. Mice on HFHCD and HFD display liver damage consistent with NASH, which was validated pathohistologically. NE activity in blood significantly increases after six weeks indicating systemic NETs involvement. In vivo imaging confirms NE activity in multiple organs. Cellular localization reveals NETs persistence even after neutrophil destruction in splenocytes indicating systemic involvement. Neutrophils under HFHCD exhibit a functional phenotype associated with low-grade inflammation, higher basal ROS levels and reduced activation potential. This study establishes the systemic impact of NETs in HFHCD- and HFD-induced liver inflammation, providing insights into the functional state of neutrophils. The findings contribute to understanding the mechanisms underlying chronic liver conditions and may inform future therapeutic strategies.
Immunological mechanisms of increased susceptibility to COVID-19 disease and its severe course in patients with diabetes mellitus type 2 and obesity
K. P. Zak1, M. D. Tronko1, S. V. Komisarenko2*
1V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: svk@biochem.kiev.ua
Received: 28 April 2023; Revised: 28 May 2023;
Accepted: 05 June 2023; Available on-line: 20 June 2023
In this review, we analyze and summarize literature data and the results of our own research related to the immunity status of patients with type 2 diabetes mellitus (T2D) and those T2D patients who were infected with the SARS-CoV-2 virus. It was shown that in the blood plasma of T2D patients, especially those with elevated BMI, the level and ultrastructure of the main cellular components of natural immunity – neutrophils and monocytes – were affected accompanied by high levels of proinflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α). It was suggested that the increased susceptibility of T2D patients to SARS-CoV-2 infection is primarily due to a weakening of the innate immune defense against pathogens, whereas in T2D patients who have COVID-19, adaptive T-cell immunity disorders accompanied by a cytokine storm prevail. It was concluded that hyperinflammation in T2D+COVID19 patients is the result of enhancement of already existing before SARS-CoV-2 infection T2D-caused disorders of innate and adaptive immunity, in the mechanism of which cytokines and chemokines play a significant role.