Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients
The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes,...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13574 |
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| author | Elżbieta Skrzydlewska Wojciech Łuczaj Michał Biernacki Piotr Wójcik Iwona Jarocka-Karpowicz Biserka Orehovec Bruno Baršić Marko Tarle Marta Kmet Ivica Lukšić Zlatko Marušić Georg Bauer Neven Žarković |
| author_facet | Elżbieta Skrzydlewska Wojciech Łuczaj Michał Biernacki Piotr Wójcik Iwona Jarocka-Karpowicz Biserka Orehovec Bruno Baršić Marko Tarle Marta Kmet Ivica Lukšić Zlatko Marušić Georg Bauer Neven Žarković |
| author_sort | Elżbieta Skrzydlewska |
| collection | DOAJ |
| description | The aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC–MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient. |
| first_indexed | 2024-03-10T23:20:09Z |
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| id | doaj.art-134f53e569bc45e9b0e60ef46994ce73 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:20:09Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-134f53e569bc45e9b0e60ef46994ce732023-11-19T08:19:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124171357410.3390/ijms241713574Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 PatientsElżbieta Skrzydlewska0Wojciech Łuczaj1Michał Biernacki2Piotr Wójcik3Iwona Jarocka-Karpowicz4Biserka Orehovec5Bruno Baršić6Marko Tarle7Marta Kmet8Ivica Lukšić9Zlatko Marušić10Georg Bauer11Neven Žarković12Department of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandDepartment of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, PolandClinical Hospital Dubrava, HR-10000 Zagreb, CroatiaClinical Hospital Dubrava, HR-10000 Zagreb, CroatiaClinical Hospital Dubrava, HR-10000 Zagreb, CroatiaClinical Hospital Dubrava, HR-10000 Zagreb, CroatiaClinical Hospital Dubrava, HR-10000 Zagreb, CroatiaDivision of Pathology, Clinical Hospital Centre Zagreb, HR-10000 Zagreb, CroatiaInstitute of Virology, Medical Center–University of Freiburg, 79104 Freiburg, GermanyLaboratory for Oxidative Stress (LabOS), Ruđer Bošković Institute, HR-10000 Zagreb, CroatiaThe aim of this study was to evaluate selected parameters of redox signaling and inflammation in the granulocytes of COVID-19 patients who recovered and those who died. Upon admission, the patients did not differ in terms of any relevant clinical parameter apart from the percentage of granulocytes, which was 6% higher on average in those patients who died. Granulocytes were isolated from the blood of 15 healthy people and survivors and 15 patients who died within a week, and who were selected post hoc for analysis according to their matching gender and age. They differed only in the lethal outcome, which could not be predicted upon arrival at the hospital. The proteins level (respective ELISA), antioxidant activity (spectrophotometry), and lipid mediators (UPUPLC–MS) were measured in the peripheral blood granulocytes obtained via gradient centrifugation. The levels of Nrf2, HO-1, NFκB, and IL-6 were higher in the granulocytes of COVID-19 patients who died within a week, while the activity of cytoplasmic Cu,Zn-SOD and mitochondrial Mn-SOD and IL-2/IL-10 were lower in comparison to the levels observed in survivors. Furthermore, in the granulocytes of those patients who died, an increase in pro-inflammatory eicosanoids (PGE2 and TXB2), together with elevated cannabinoid receptors 1 and 2 (associated with a decrease in the anti-inflammatory 15d-PGJ2), were found. Hence, this study suggests that by triggering transcription factors, granulocytes activate inflammatory and redox signaling, leading to the production of pro-inflammatory eicosanoids while reducing cellular antioxidant capacity through SOD, thus expressing an altered response to COVID-19, which may result in the onset of systemic oxidative stress, ARDS, and the death of the patient.https://www.mdpi.com/1422-0067/24/17/13574antioxidantsCOVID-19eicosanoidsG protein-coupled receptorsgranulocytesinflammation |
| spellingShingle | Elżbieta Skrzydlewska Wojciech Łuczaj Michał Biernacki Piotr Wójcik Iwona Jarocka-Karpowicz Biserka Orehovec Bruno Baršić Marko Tarle Marta Kmet Ivica Lukšić Zlatko Marušić Georg Bauer Neven Žarković Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients International Journal of Molecular Sciences antioxidants COVID-19 eicosanoids G protein-coupled receptors granulocytes inflammation |
| title | Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients |
| title_full | Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients |
| title_fullStr | Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients |
| title_full_unstemmed | Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients |
| title_short | Preliminary Comparison of Molecular Antioxidant and Inflammatory Mechanisms Determined in the Peripheral Blood Granulocytes of COVID-19 Patients |
| title_sort | preliminary comparison of molecular antioxidant and inflammatory mechanisms determined in the peripheral blood granulocytes of covid 19 patients |
| topic | antioxidants COVID-19 eicosanoids G protein-coupled receptors granulocytes inflammation |
| url | https://www.mdpi.com/1422-0067/24/17/13574 |
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