Leo Nicolai

Same here @dianvanderwaldr.bsky.social was a pleasure giving the State of the Art talk on platelet immune effector functions @isth.org #isth2025

#platelets keep surprise me @immunothrombosis.bsky.social as always great imaging

#isth2025 and very interesting par1 signalling in lymphatic endothelial bed SOA7

Online now: Yacine Boulaftali, Steffen Massberg and I summarized recent key insights into the role of platelets in vascular inflammation:
journals.lww.com/co-hematolog...

Thanks for the support @lmumuenchen.bsky.social hen.bsky.social @dzhk.de , Corona Foundation, and all the fantastic contributors, in particular Kami Pekayvaz and Konstantin Stark.

Interfering with either cell type worsens thrombosis in mice. Happy to discuss these unexpected results. And I'm inviting the field to look into our data set for novel anti thrombotic targets and strategies!

Using in vitro assays and reverse translation into mice, we could show that alternative monocytes are indeed responsible for neutrophil recruitment. Neutrophils then adopt a hypoxia-induced thrombus-resolving urokinase receptor (PLAUR)+ phenotype.

Suprisingly, we found thrombolytic signatures in neutrophils, and a significant amount of alternative monocytes expressing neutrophil attracting chemokines.

Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution Thrombotic diseases remain the major cause of death and disability worldwide, and the contribution of inflammation is increasingly recognized. Thrombo…

Immune cells contribute to thrombosis in mouse models - but what about human disease? We used scRNA Sequencing, flow cytometry and histology to better understand immune cells in human stroke thrombi www.sciencedirect.com/science/arti... now online @cp-immunity.bsky.social

Immunothrombolytic monocyte-neutrophil axes dominate the single-cell landscape of human thrombosis and correlate with thrombus resolution Thrombotic diseases remain the major cause of death and disability worldwide, and the contribution of inflammation is increasingly recognized. Thrombo…

#TheMoreTheMerrier! Pekayvaz @immunothrombosis.bsky.social Stark &co show @cp-immunity.bsky.social that non-classical monocytes help to resolve thrombi by recruiting neutrophils that become thrombolytic following hypoxia-induced programs!
www.sciencedirect.com/science/arti...

Aging platelets shift their hemostatic properties to inflammatory functions Key PointsPlatelets change their phenotype as they age in circulation, skewing toward inflammatory function over time.Genetic models of increased platelet

Very happy to contribute another @bloodjournal.bsky.social cover with our story on aging platelets:
ashpublications.org/blood/articl...
Thoughtful commentary by Laura Gutiérrez in the issue as well.

Thanks Alex

A pleasure to work with you - looking forward to completing our ongoing cooperation projects !

Thanks Beth

14/x Thanks for the support LMU, DZHK, Corona Foundation, and all the fantastic contributors

13/x It is now key to understand the regulating mechanisms, as well as its implications for transfusion medicine – vulnerable populations might be negatively affected by platelet transfusions of prolonged storage time. Happy to discuss!

12/x We could also observe a proinflammatory effect of in vitro aged platelets in comparison to fresh platelets in a mouse model of thrombocytopenia and pulmonary inflammation. This suggests that platelets undergo gradual changes, with aged platelets showing a more inflammatory profile.

11/x We then asked if this also applies to human platelet concentrates stored in vitro. Indeed, apheresis platelets also showed a decrease in hemostatic potential and an increase in procoagulant function and neutrophil aggregate formation.

10/x Importantly, these mice showed increased pulmonary inflammation with elevated cytokines and an increased leukocyte recruitment, which could be reversed through platelet rejuvenation. This showcases that aged platelets can indeed exacerbate inflammation.

9/x To investigate effects of this, we teamed up with @frederikdenorme.bsky.social and Robert Campbell, who subjected Bax/Bak deficient mice to acute lung injury. This mouse model is known to harbor platelets with increased life span due to an apoptotic defect.

8/x As expected, young platelets showed upregulation of ribosomal proteins. The aged cohort showed upregulation of immune pathways, correlating well with our in vivo and in vitro results.

7/x Using the PF4Cre-iDTR mouse, we created platelet cohorts of similar age using Diphtheria toxin application in this mouse line, and performed shotgun proteomics. This revealed clear separation of aged and young platelets with regards to proteome.

6/x We then asked if this translates to in vivo differences. Indeed, in thrombosis, more young platelets were recruited, whereas in an assay of lung inflammation, there was higher relative recruitment of aged platelets.

5/x ..and formed more platelet neutrophil aggregates upon co-incubation, which could be blocked by antibodies against CD40. These platelets were also better at killing S. Aureus bacteria in vitro.

4/x Interestingly, though, aged platelets (3-4 days old) showed increased expression of immune related receptors including CD40L and CLEC-2. They were more likely to become procoagulant,

3/x Here, using an antibody-based fate mapping approach, we were able to directly demonstrate that young platelets (0-12hrs old) are better at adhesion and clot formation in vitro. This fits well with translational data implicating young, reticulated platelets for example in myocardial infarction.

2/x Platelet are crucial players not only in thrombosis and hemostasis but also in inflammation. Therefore, a central question is if subsets of platelets exist that specialize in some tasks. Also, the fate of platelets once released from the bone marrow remains elusive.

1/x Online now: Our work on platelet aging and inflammation in @bloodjournal.bsky.social led by superstar PhD student Afra Anjum: ashpublications.org/blood/articl...

Arterial thrombosis - studying platelet recruitment at the single cell level in vivo

It was an immense pleasure to host our 2nd #immunothrombosis Symposium @LMU Munich
together with Konstantin Stark. Talks and discussions were outstanding, and new ideas & perspectives made the meeting really special!