Molecular Sciences I. Posters
Fige, Éva
Department of Biochemistry and Molecular Biology, University of Debrecen
06205015548
fige.eva@med.unideb.hu
Macrophage Heme Oxygenase-1 in the Clearance of Apoptotic Cells
Éva Fige1,2 Zsuzsa Szondy2,3,
1Doctoral School of Dental Sciences, University of Debrecen, Debrecen, Hungary
2Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
3Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary
Molecular Sciences I. Posters
English
Molecular Sciences
Health Sciences
Every day billions of cells die in our body to eliminate those that are harmful, useless or senescent. Uncleared apoptotic corpses can promote inflammation, so their rapid and non-immunogenic removal is essential for maintaining tissue homeostasis. Heme is important for all aerobic cells, although it can be poisonous in a non-protein-bound form. Disposal of heme is important for preventing heme and iron-mediated cellular toxicity. Heme oxygenase-1 (HO-1) is an inducible microsomal enzyme that catalyzes the first and rate-limiting step in heme degradation.
A previous research in our laboratory has shown that HO-1 mRNA level was increased in wild type bone marrow-derived macrophages (BMDMs) after incubation with apoptotic thymocytes (aT). Thus we decided to investigate the role of HO-1 in the engulfment program.
In our experiments, we measured HO-1 induction in wild type BMDMs that were incubated with aTs, apoptotic red blood cells (aRBCs) or with their supernatant alone, in the presence of HO-1 inhibitor or an engulfment inhibitor. We were curious wether inhibition of HO-1 activity, thus lack of heme degradation affects phagocytosis. Percentage of engulfing BMDMs was determined after 30 minutes, 7 or 25 hours incubation with apoptotic cells. Finally, we studied the effect of HO-1 inhibition on the cytokine profile of resting and apoptotic cell treated BMDMs.
The uptake of both apoptotic cell types induce HO-1 expression in macrophages. Even if phagocytosis is inhibited, the HO-1 mRNA level is increased in the presence of aTs, but not in case of aRBCs, indicating that aTs mainly use extracellular signals regulate HO-1 expression. No difference was found during short-term or mid-term phagocytosis of apoptotic cells in the absence of HO-1 activity. However, when the time of phagocytosis was increased, less aRBCs were engulfed by macrophages in the presence of HO-1 inhibitor. Normally clearance of apoptotic cells is an immunologically silent process. However, when BMDMs were exposed to aRBCs in the presence of HO-1 inhibitor, we found that the expression of some pro-inflammatory cytokines were increased.
Our data indicate that different dead cells might use different mechanisms for inducing HO-1: low heme-containing apoptotic thymocytes mainly use extracellular pathway, while high heme-containing aRBCs mainly use intracellular HO-1 induction pathway.
Zsuzsa Szondy
szondy@med.unideb.hu
EFOP-3.6.3-VEKOP-16-2017-00009 „Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése"
Poszter
Szabad
elfogadva
poszter
nem rendelkezett róla
4765
11:35
11:38
Éva Fige1,2 Zsuzsa Szondy2,3,
1Doctoral School of Dental Sciences, University of Debrecen, Debrecen, Hungary
2Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
3Department of Basic Medical Sciences, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary