Neutrophils scan for activated platelets to initiate inflammation

Science 5 December 2014: 
Vol. 346 no. 6214 pp. 1234-1238 
DOI: 10.1126/science.1256478

• REPORT

Neutrophils scan for activated platelets to initiate inflammation

1. Vinatha Sreeramkumar1, 
2. José M. Adrover1, 
3. Ivan Ballesteros2, 
4. Maria Isabel Cuartero2, 
5. Jan Rossaint3,
6. Izaskun Bilbao1,4, 
7. Maria Nácher1,5, 
8. Christophe Pitaval1, 
9. Irena Radovanovic1, 
10. Yoshinori Fukui6, 
11. Rodger P. McEver7,
12. Marie-Dominique Filippi8, 
13. Ignacio Lizasoain2, 
14. Jesús Ruiz-Cabello1,4, 
15. Alexander Zarbock3, 
16. María A. Moro2,
17. Andrés Hidalgo1,9,*

+Author Affiliations

1. ¹Department of Atherothrombosis, Imaging and Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
2. ²Unidad de Investigación Neurovascular, Department of Pharmacology, Faculty of Medicine, Universidad Complutense and Instituto de Investigación Hospital 12 de Octubre (i+12), Madrid, Spain.
3. ³Department of Anesthesiology and Critical Care Medicine, University of Münster and Max Planck Institute Münster, Münster, Germany.
4. ⁴Ciber de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
5. ⁵Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Australia.
6. ⁶Division of Immunogenetics, Department of Immunobiology and Neuroscience, Kyushu University, Japan.
7. ⁷Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
8. ⁸Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
9. ⁹Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Munich, Germany.

1. ↵*Corresponding author. E-mail: ahidalgo@cnic.es

• ABSTRACT
• EDITOR'S SUMMARY

Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils’ bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.

• Received for publication 27 May 2014.
• Accepted for publication 7 November 2014.

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