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Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury

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Hidalgo, Andrés, Chang, Jungshan, Jang, Jung-Eun, Peired, Anna J, Chiang, Elaine Y, Frenette, Paul S·2009·Nature Medicine
DOI 10.1038/nm.1939
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Abstract

Selectins and their ligands mediate leukocyte rolling, allowing interactions with chemokines that lead to integrin activation and arrest. Here we show that E-selectin is crucial for generating a secondary wave of activating signals, transduced specifically by E-selectin ligand-1, that induces polarized, activated αMβ2 integrin clusters at the leading edge of crawling neutrophils, allowing capture of circulating erythrocytes or platelets. In a humanized mouse model of sickle cell disease, the capture of erythrocytes by αMβ2 microdomains leads to acute lethal vascular occlusions. In a model of transfusion-related acute lung injury, polarized neutrophils capture circulating platelets, resulting in the generation of oxidative species that produce vascular damage and lung injury. Inactivation of E-selectin or αMβ2 prevents tissue injury in both inflammatory models, suggesting broad implications of this paradigm in thromboinflammatory diseases. These results indicate that endothelial selectins can influence neutrophil behavior beyond its canonical rolling step through delayed, organ-damaging, polarized activation.

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Metadata

Authors
Hidalgo, A., Chang, J., Jang, J.-E., Peired, A. J., Chiang, E. Y., & Frenette, P. S.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2009-03-22
Volume
15
Issue
4
Pages
384-391
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.1939
OpenAlex
W2137744809
Cited by
358
References
2
FWCI
18.12
Type
journal article
Language
en
Open access
green
Licence
www.springer.com/tdm (tdm)

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Hidalgo, A., Chang, J., Jang, J.-E., Peired, A. J., Chiang, E. Y., & Frenette, P. S. (2009). Heterotypic interactions enabled by polarized neutrophil microdomains mediate thromboinflammatory injury. Nature Medicine. https://doi.org/10.1038/nm.1939

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