PhD Scientific Days 2020

Theoretical and Translational V. Lectures

The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response upon Intraventricular Hemorrhage in Premature Infants

Előadó neve

Erdei, Judit, MSc

Előadó munkahelye

Research Centre for Molecular Medicine, University of Debrecen

Előadó telefonszáma

+36307201606

Előadó e-mail címe

jutka.erdei@med.unideb.hu

Az előadás címe

The Role of Hemoglobin Oxidation Products in Triggering Inflammatory Response upon Intraventricular Hemorrhage in Premature Infants

Szerző(k) neve és munkahelye

Judit Erdei1,2, Andrea Tóth1,2, Andrea Nagy3, Benard Bogonko Nyakundi1,2, Enikő Balogh1, Viktória Jeney1

1: MTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2: Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
3: Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

Szekció

Theoretical and Translational V. Lectures

Language of the presentation

English

Section, first choice

Theoretical and Translational Medicine

Section, second choice

Molecular Sciences

Összefoglaló szövege

Introduction: Intraventricular hemorrhage (IVH) is a frequent complication of prematurity that is associated with high neonatal mortality and morbidity. IVH is accompanied by red blood cell (RBC) lysis, hemoglobin (Hb) oxidation, and sterile inflammation. Recent studies showed extracellular Hb, methemoglobin (metHb) and heme to be involved in inflammation following IVH. They also highlighted the role of Hb oxidation and heme release in inflammation after the onset of IVH.

Aims: Our goal was to perform a qualitative and quantitative analysis of Hb content of human cerebrospinal fluid (CSF) collected from premature infants after the onset of IVH. We also wanted to investigate the pro-oxidant and pro-inflammatory effects of Hb forms on human brain microvascular endothelial cells.

Methods: We collected cerebrospinal fluid (N=20) from premature infants with grade III IVH at different time points after the onset of IVH. Levels of Hb, metHb, and ferrylHb were determined by analysis of the visible spectra of CSF samples. Oxidative Hb crosslinking was assessed by Western blot. Concentrations of soluble adhesion molecules VCAM-1, and
ICAM-1 and the pro-inflammatory cytokine IL-8 in CSF were determined by ELISA. Our in vitro experiments were performed on human brain microvascular endothelial cells (HBECs).

Results: Levels of Hb, metHb, total heme and free heme were the highest in CSF samples obtained between days 0-20 after the onset of IVH and were mostly non-detectable in CSF collected between days 41-60 of post-IVH. Besides Hb monomers, we detected crosslinked Hb dimers and tetramers in post-IVH CSF samples obtained in days 0-20 and 21-40, but only Hb tetramers were detected in CSF samples obtained after 41-60 days. VCAM-1 and IL-8 levels were higher in CSF samples obtained between days 0-20 than in CSF samples collected between days 41-60 of post-IVH. Applying free heme and oxidized Hb forms on human brain microvascular endothelial cells revealed, that free heme induces cell death whereas oxidized Hb forms in particularly ferrylHb triggers an inflammatory response.

Conclusions: We concluded that RBC lysis, Hb oxidation and heme release play important roles in the inflammatory response following IVH. However, the pathogenic role of covalently crosslinked Hb multimers need to be further investigated.

Additional Information

Supervisor: Viktória Jeney
E-mail address: jeney.viktoria@med.unideb.hu


EFOP-3.6.3-VEKOP-16-2017-00009

Bemutatás módja

Szóbeli

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4701

Start

17:15

End

17:30

Authors (legacy)

Judit Erdei1,2, Andrea Tóth1,2, Andrea Nagy3, Benard Bogonko Nyakundi1,2, Enikő Balogh1, Viktória Jeney1

1: MTA-DE Lendület Vascular Pathophysiology Research Group, Research Centre for Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
2: Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
3: Department of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary