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Ontstekingscellen the good and the bad guy. Endogline heterozygoten herstellen slecht na schade MNC isolation Myocardial infarction Mouse-cardio- MRI.

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Presentatie over: "Ontstekingscellen the good and the bad guy. Endogline heterozygoten herstellen slecht na schade MNC isolation Myocardial infarction Mouse-cardio- MRI."— Transcript van de presentatie:

1 Ontstekingscellen the good and the bad guy

2 Endogline heterozygoten herstellen slecht na schade MNC isolation Myocardial infarction Mouse-cardio- MRI Laake LW van et al, Circulation 2006 Nov 21;114(21):

3 Monday, July 21, Wat gebeurd er na een hartaanval

4 Monday, July 21, Een ontsteking en herstel fase

5 Monday, July 21, Wat voor ontstekingscellen zijn er ?

6 HHT-1 MNCs: minder vaten en minder cellen Control HHT-1 Control HHT-1 PBS # Human-UEA+ cells Laake LW van et al, Circulation 2006 Nov 21;114(21):

7 Monday, July 21, Waarom zijn er minder cellen in het hart Post, CVR, 2010 Circulating MNCs attracted to injury Chemokine receptors

8 Monday, July 21, Aantal monocyten in het bloed is gelijk Post, CVR, 2010

9 Monday, July 21, Niveau van CD26/DPP-IV is hoog Post, CVR, 2010

10 Monday, July 21, CD26/DPP-IV remt homing van cellen naar schade Post, CVR, 2010 ↑SDF-1α 1 day post-MI CXCR4: receptor for SDF-1 CD26= Dipeptidyl peptidase:cleaves SDF-1 and internalize CXCR4 SDF-1  Increased after MI MNC Homing + CXCR4+ MNC - Homing CXCR4+ CD26+

11 Monday, July 21, CD26/DPP-IV remt migratie in vitro Post, CVR, 2010 Expression of CD26 on MNC of HHT patients was inversely correlated with migration capacity Decrease in migration capacity of HHT1-MNC

12 Monday, July 21, CD26 remming stimuleert migratie in vitro A Post, CVR, 2010

13 Monday, July 21, CD26/DPP-IV inhibitie stimuleert migratie van gezonde en HHT cellen

14 Monday, July 21, Systemische CD26/DPP-IV remming stimuleert homing van circulerende monocyten Sitagliptin MONOCYTEN

15 Monday, July 21, Macrofagen en weefsel herstel Na schade zijn er 2 fase van macrofaag influx Phase I: vroege invasie van inflammatie macrofagen (M1)  Degradatie van beschadigd weefsel Phase II: Niet inflammatoire macrofagen (M2)  Regeneratieve capacity Days after injury % maximum Phase I Phase II M1 M2 InflammatoryRegenerative

16 Monday, July 21, Wat doen M2 macrofagen

17 Maturatie van macrofagen Monday, July 21, /- GM-CSF (Macrophage differentiation) Inflammatie status Based on expression of Ly6C on macrophages M1: Inflammatory mph M2: Anti-inflammatory mph

18 Maturatie van macrofagen in vivo Monday, July 21, Spleen Monocytes M2 macrophages Muscle Eng+/+Muscle Eng+/- CD11b / DAPI (MR = Mannose receptor or CD206) MR / DAPI

19 Hoe beinvloed TGFb macrofaag maturatie? Monday, July 21, TGFβ M1 Inflammatory M2 Regenerative ? Low CD206 expression High CD206 expression - GM-CSF - GM-CSF + TGFβ 24h - GM-CSF + TGFβ 4 days

20 TGFb speelt met de balans tussen M1 en M2 Monday, July 21, Regenerative status Based on expression of Mannose Receptor (CD206) on macrophages

21 Dus…. Monday, July 21, Eng+/-

22 Vinden we dit nu alleen in muis? Monday, July 21, Human Monocyte/macrophage markers: 1. CD14 ++ / CD16-  Immature monocytes 2. CD14+/ CD16+  Pro-inflammatory macrophages 3. CD14++ / CD16+  Regenerative macrophages 1. Immature 2. Pro-inflammatory 3. Regenerative

23 Monday, July 21, Conclusie Ontstekingscellen voor herstel TGFb/Endoglin is crucial voor bloedvatvorming TGFb/Endoglin is homen van circulerende cellen en vorming van herstellende macrofagen.

24 Toekomst Monday, July 21,

25 25 Thanks to: UMCU, Experimental Cardiology Simone Post Sandra van den Broek Imo Hoefer Hubrecht laboratory Linda van Laake Franck Lebrin St. Antonius Hospital, Nieuwegein Hans Mager Repke Snijder Cees Westermann All patients en healthy controls for their blood donations LUMC Dept. Mol. Cell Biol., Anke Smits Wineke Bakker Peter ten Dijke Dept. Anatomy & Embryology, Christine Mummery


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