Thank you for attending THSNA 2026. The virtual meeting is now closed.
| Triad of Platelets, NETs, and Sepsis Kandace Gollomp. |
Abstract
Sepsis is a life-threatening condition characterized by dysregulated host responses to infection. We now identify platelet factor 4 (PF4) as a key mediator of vascular antimicrobial defense. In vitro, PF4 enhanced endothelial cell internalization of Escherichia coli via interactions with the PF4 receptor CXCR3 and the endothelial glycocalyx, directing bacteria to clathrin-mediated endocytosis and lysosomal degradation. In vivo, PF4 administration improved survival and reduced sepsis severity, bacterial burden, inflammation, and thrombosis in wild-type (WT) and PF4 knockout (PF4) mice challenged with systemic polymicrobial infection. Using intravital microscopy, we observed that infused bacteria were rapidly sequestered in the lung vasculature; however, PF4 knockout mice exhibited impaired bacterial clearance and increased microvascular platelet aggregation and adhesion. In the liver, following Kupffer cell depletion, PF4 mice had increased sinusoidal platelet accumulation, larger bacterial aggregates, and elevated hepatic bacterial burden compared to WT controls. Together, these findings reveal that PF4 promotes bacterial clearance and restrains immunothrombosis during sepsis. By enhancing endothelial antimicrobial function, PF4 represents a previously underappreciated host defense mechanism that may limit bacterial dissemination and reduce vascular injury during infection.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.