Thromb Haemost 2022; 122(04): 517-528
DOI: 10.1055/s-0041-1731288
Cellular Haemostasis and Platelets

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

Gabrielle J. Pennings
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Caroline J. Reddel
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Mathew Traini
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Magdalena Lam
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Maaike Kockx
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
,
Vivien M. Chen
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
2   Department of Haematology, Concord Repatriation General Hospital, Sydney Local Health District, New South Wales, Australia
,
Leonard Kritharides
1   Vascular Biology Group, ANZAC Research Institute, Concord Repatriation General Hospital, University of Sydney, Concord, New South Wales, Australia
3   Department of Cardiology, Concord Repatriation General Hospital, Sydney Local Health District, New South Wales, Australia
› Author Affiliations
Funding This work was supported by the Balnaves Foundation and Sydney Medical School with Kick Start Grants (C.R. and G.J.P.), and National Health and Medical Research Council [NHMRC Program grant number 1037903] (L.K.), and NSW Department of Health CV Research Grant to L.K.

Abstract

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.

Supplementary Material



Publication History

Received: 07 December 2020

Accepted: 07 May 2021

Article published online:
25 June 2021

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