TY - JOUR
T1 - Platelet-derived integrin- and tetraspanin-enriched tethers exacerbate severe inflammation
AU - Kusch, Charly
AU - Stegner, David
AU - Weiss, Lukas J.
AU - Nurden, Paquita
AU - Burkard, Philipp
AU - Johnson, Denise
AU - Bergmeier, Wolfgang
AU - Onursal, Ceylan
AU - Navarro, Stefano
AU - Hackenbroch, Christian
AU - Pfeiffer, Dennis
AU - Bonfiglio, Sabrina Ivana
AU - Meub, Mara
AU - Gross, Carina
AU - Schenk, Joachim
AU - Fumagalli, Valeria
AU - Mott, Kristina
AU - Bender, Markus
AU - Iannacone, Matteo
AU - Andres, Oliver
AU - Kastenmüller, Wolfgang
AU - Heinze, Katrin G.
AU - Sauer, Markus
AU - Schulze, Harald
AU - Ley, Klaus
AU - Nurden, Alan T.
AU - Nieswandt, Bernhard
N1 - Publisher Copyright:
Copyright © 2026 the authors, some rights reserved.
PY - 2026/1/22
Y1 - 2026/1/22
N2 - Platelet integrin αIIbβ3 is essential for hemostasis, thrombosis, and inflammation. We found that ligation of αIIbβ3 by von Willebrand factor or fibrin under flow triggered its accumulation in plasma membrane extensions or “platelet-derived integrin- and tetraspanin-enriched tethers” (PITTs). PITTs remained anchored to leukocytes or endothelial cells, whereas the partially αIIbβ3-deficient platelet body detached. although still responsive to stimuli, αIIbβ3-deficient platelets did not support thrombus formation. PITTs promoted leukocyte activation and vascular inflammation in mouse models of infection and endotoxemia, and αIIbβ3 blockade reduced immune-mediated tissue damage. In patients with sepsis, COVID-19, or severe infections, PITT formation and platelet αIIbβ3 loss correlated with disease severity and adverse outcomes. We propose that PITTs are proinflammatory structures that amplify immune responses while contributing to platelet dysfunction in thrombo-inflammatory disease.
AB - Platelet integrin αIIbβ3 is essential for hemostasis, thrombosis, and inflammation. We found that ligation of αIIbβ3 by von Willebrand factor or fibrin under flow triggered its accumulation in plasma membrane extensions or “platelet-derived integrin- and tetraspanin-enriched tethers” (PITTs). PITTs remained anchored to leukocytes or endothelial cells, whereas the partially αIIbβ3-deficient platelet body detached. although still responsive to stimuli, αIIbβ3-deficient platelets did not support thrombus formation. PITTs promoted leukocyte activation and vascular inflammation in mouse models of infection and endotoxemia, and αIIbβ3 blockade reduced immune-mediated tissue damage. In patients with sepsis, COVID-19, or severe infections, PITT formation and platelet αIIbβ3 loss correlated with disease severity and adverse outcomes. We propose that PITTs are proinflammatory structures that amplify immune responses while contributing to platelet dysfunction in thrombo-inflammatory disease.
UR - https://www.scopus.com/pages/publications/105028619679
UR - https://www.scopus.com/pages/publications/105028619679#tab=citedBy
U2 - 10.1126/science.adu2825
DO - 10.1126/science.adu2825
M3 - Article
AN - SCOPUS:105028619679
SN - 0036-8075
VL - 391
JO - Science
JF - Science
IS - 6783
ER -