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Leo Nicolai @immunothrombosis.bsky.social · Jun 22

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

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Reposted by Leo Nicolai

Dianne @dianvanderwaldr.bsky.social · Jun 22

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

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

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Leo Nicolai @immunothrombosis.bsky.social · May 19

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...

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Leo Nicolai @immunothrombosis.bsky.social · Apr 24

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.

Leo Nicolai @immunothrombosis.bsky.social · Apr 24

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!

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Leo Nicolai @immunothrombosis.bsky.social · Apr 24

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.

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Leo Nicolai @immunothrombosis.bsky.social · Apr 24

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

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Leo Nicolai @immunothrombosis.bsky.social · Apr 24

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…

www.sciencedirect.com

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Reposted by Leo Nicolai

Ivan Zanoni @lozanzi.bsky.social · Apr 24

#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...

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…

www.sciencedirect.com

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Leo Nicolai @immunothrombosis.bsky.social · Apr 3

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.

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

ashpublications.org

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Leo Nicolai @immunothrombosis.bsky.social · Jan 25

Thanks Alex

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Leo Nicolai @immunothrombosis.bsky.social · Jan 25

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

Leo Nicolai @immunothrombosis.bsky.social · Jan 25

Thanks Beth

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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!

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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,

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Leo Nicolai @immunothrombosis.bsky.social · Jan 23

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.

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