iiinova — where your digital self keeps evolving

Leo Nicolai @immunothrombosis.bsky.social · 22/06/2025

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

020

Leo Nicolai @immunothrombosis.bsky.social · 19/05/2025

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...

080

Leo Nicolai @immunothrombosis.bsky.social · 24/04/2025

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.

010

Leo Nicolai @immunothrombosis.bsky.social · 24/04/2025

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!

110

Leo Nicolai @immunothrombosis.bsky.social · 24/04/2025

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.

100

Leo Nicolai @immunothrombosis.bsky.social · 24/04/2025

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

110

Leo Nicolai @immunothrombosis.bsky.social · 25/01/2025

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

000

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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

020

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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!

120

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

110

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

110

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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,

121

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

120

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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.

110

Leo Nicolai @immunothrombosis.bsky.social · 23/01/2025

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...

2319

Leo Nicolai @immunothrombosis.bsky.social · 21/11/2024

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

4354

Leo Nicolai @immunothrombosis.bsky.social · 21/11/2024

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!

040