Neutrophil infiltration to the brain is platelet-dependent, and is reversed by blockade of platelet GPIbα

James A Giles, Andrew D Greenhalgh, Adam Denes, Bernhard Nieswandt, Graham Coutts, Barry W McColl, Stuart M Allan

Research output: Contribution to journalArticlepeer-review

Abstract

Neutrophils are key components of the innate immune response, providing host defence against infection and being recruited to non-microbial injury sites. Platelets act as a trigger for neutrophil extravasation to inflammatory sites but mechanisms and tissue-specific aspects of these interactions are currently unclear. Here, we use bacterial endotoxin in mice to trigger an innate inflammatory response in different tissues and measure neutrophil invasion with or without platelet reduction. We show that platelets are essential for neutrophil infiltration to the brain, peritoneum and skin, neutrophil numbers returning to basal levels in the peritoneum and skin and being decreased (~60%) in the brain when platelets are reduced. In contrast neutrophil infiltration in the lung is unaffected by platelet reduction, up-regulation of CXCL-1 (2.4-fold) and CCL5 (1.4-fold) acting as a compensatory mechanism in platelet-reduced mice during lung inflammation. In brain inflammation targeting platelet receptor GPIbα results in a significant decrease (44%) in platelet-mediated neutrophil invasion, whilst maintaining platelet numbers in the circulation. These results suggest that therapeutic blockade of platelet GPIbα could limit the harmful effects of excessive inflammation while minimising haemorrhagic complications of platelet reduction in the brain. The data also demonstrate the ability to target damaging brain inflammation in stroke and related disorders without compromising lung immunity and hence risk of pneumonia, a major complication post-stroke. In summary, our data reveal an important role for platelets in neutrophil infiltration to various tissues, including the brain, and so implicate platelets as a key, targetable component of cerebrovascular inflammatory disease or injury. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)322-328
Number of pages7
JournalImmunology
Volume154
Issue number2
Early online date11 Jan 2018
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Journal Article

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