Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase.

Thromb Haemost

Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia.

Published: April 2022

Objective:  Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.

Methods And Results:  Using flow cytometry to detect platelet activation (and release of α and dense granule contents) and the combination of Western blotting, enzyme-linked-immunosorbent assay, and immunogold labeling transmission electron and immunofluorescence microscopy, we identified that resting human platelets contain mature IL-1β. Platelets release IL-1β within minutes in response to adenosine diphosphate (ADP), collagen, and thrombin receptor agonists, but not in response to conventional NLRP3 inflammasome agonists-lipopolysaccharide and adenosine triphosphate. The rapid release of IL-1β in response to ADP and thrombin receptor agonists was independent of caspases (including caspase-1) and NLRP3. Immature and mature IL-1β were identified as low-abundance proteins on transmission electron microscopy of human platelets, and were localized to the platelet cytosol, open canalicular system, and the periphery of α granules.

Conclusion:  Unlike monocytes and neutrophils, human platelets are capable of rapid agonist- and time-dependent release of IL-1β by a mechanism which is independent of caspase-1 and NLRP3.

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1731288DOI Listing

Publication Analysis

Top Keywords

rapid release
16
human platelets
16
release il-1β
16
release
8
il-1β
8
nlrp3 inflammasome
8
il-1β response
8
transmission electron
8
mature il-1β
8
thrombin receptor
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!