Platelet-monocyte Aggregates: Molecular Mediators of Thromboinflammation

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2023 May 31

PMID 37255704

Authors

Christina C Rolling

Tessa J Barrett

Jeffrey S Berger

Affiliations

Soon will be listed here.

Abstract

Platelets, key facilitators of primary hemostasis and thrombosis, have emerged as crucial cellular mediators of innate immunity and inflammation. Exemplified by their ability to alter the phenotype and function of monocytes, activated platelets bind to circulating monocytes to form monocyte-platelet aggregates (MPA). The platelet-monocyte axis has emerged as a key mechanism connecting thrombosis and inflammation. MPA are elevated across the spectrum of inflammatory and autoimmune disorders, including cardiovascular disease, systemic lupus erythematosus (SLE), and COVID-19, and are positively associated with disease severity. These clinical disorders are all characterized by an increased risk of thromboembolic complications. Intriguingly, monocytes in contact with platelets become proinflammatory and procoagulant, highlighting that this interaction is a central element of thromboinflammation.

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References

Margraf A, Zarbock A . Platelets in Inflammation and Resolution. J Immunol. 2019; 203(9):2357-2367. DOI: 10.4049/jimmunol.1900899. View

Leucker T, Osburn W, Reventun P, Smith K, Claggett B, Kirwan B . Effect of Crizanlizumab, a P-Selectin Inhibitor, in COVID-19: A Placebo-Controlled, Randomized Trial. JACC Basic Transl Sci. 2021; 6(12):935-945. PMC: 8653991. DOI: 10.1016/j.jacbts.2021.09.013. View

Morrell C, Aggrey A, Chapman L, Modjeski K . Emerging roles for platelets as immune and inflammatory cells. Blood. 2014; 123(18):2759-67. PMC: 4007605. DOI: 10.1182/blood-2013-11-462432. View

Hui H, Fuller K, Erber W, Linden M . Measurement of monocyte-platelet aggregates by imaging flow cytometry. Cytometry A. 2014; 87(3):273-8. DOI: 10.1002/cyto.a.22587. View

Pitsilos S, Hunt J, Mohler E, Prabhakar A, Poncz M, Dawicki J . Platelet factor 4 localization in carotid atherosclerotic plaques: correlation with clinical parameters. Thromb Haemost. 2003; 90(6):1112-20. DOI: 10.1160/TH03-02-0069. View

Singhal R, Chawla S, Batra H, Gupta S, Ojha A, Rathore D . Engulfment of Hb-activated platelets differentiates monocytes into pro-inflammatory macrophages in PNH patients. Eur J Immunol. 2018; 48(8):1285-1294. DOI: 10.1002/eji.201747449. View

Layne K, Di Giosia P, Ferro A, Passacquale G . Anti-platelet drugs attenuate the expansion of circulating CD14highCD16+ monocytes under pro-inflammatory conditions. Cardiovasc Res. 2016; 111(1):26-33. PMC: 4909161. DOI: 10.1093/cvr/cvw089. View

Steffel J, Luscher T, Tanner F . Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation. 2006; 113(5):722-31. DOI: 10.1161/CIRCULATIONAHA.105.567297. View

Japp A, Chelliah R, Tattersall L, Lang N, Meng X, Weisel K . Effect of PSI-697, a novel P-selectin inhibitor, on platelet-monocyte aggregate formation in humans. J Am Heart Assoc. 2013; 2(1):e006007. PMC: 3603266. DOI: 10.1161/JAHA.112.006007. View

10.

Oleksowicz L, Mrowiec Z, Zuckerman D, Isaacs R, Dutcher J, Puszkin E . Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost. 1994; 72(2):302-8. View

11.

Speth C, Rambach G, Wurzner R, Lass-Florl C, Kozarcanin H, Hamad O . Complement and platelets: Mutual interference in the immune network. Mol Immunol. 2015; 67(1):108-18. DOI: 10.1016/j.molimm.2015.03.244. View

12.

Kapellos T, Bonaguro L, Gemund I, Reusch N, Saglam A, Hinkley E . Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases. Front Immunol. 2019; 10:2035. PMC: 6728754. DOI: 10.3389/fimmu.2019.02035. View

13.

Boilard E, Nigrovic P, Larabee K, Watts G, Coblyn J, Weinblatt M . Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science. 2010; 327(5965):580-3. PMC: 2927861. DOI: 10.1126/science.1181928. View

14.

Offermanns S . Activation of platelet function through G protein-coupled receptors. Circ Res. 2006; 99(12):1293-304. DOI: 10.1161/01.RES.0000251742.71301.16. View

15.

Ivanov I, Apta B, Bonna A, Harper M . Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes. Sci Rep. 2019; 9(1):13397. PMC: 6746844. DOI: 10.1038/s41598-019-49635-7. View

16.

Garshick M, Tawil M, Barrett T, Salud-Gnilo C, Eppler M, Lee A . Activated Platelets Induce Endothelial Cell Inflammatory Response in Psoriasis via COX-1. Arterioscler Thromb Vasc Biol. 2020; 40(5):1340-1351. PMC: 7180109. DOI: 10.1161/ATVBAHA.119.314008. View

17.

Ye Z, Zhong L, Zhu S, Wang Y, Zheng J, Wang S . The P-selectin and PSGL-1 axis accelerates atherosclerosis via activation of dendritic cells by the TLR4 signaling pathway. Cell Death Dis. 2019; 10(7):507. PMC: 6602970. DOI: 10.1038/s41419-019-1736-5. View

18.

Mariscal A, Zamora C, Magallares B, Salman-Monte T, Ortiz M, Diaz-Torne C . Phenotypic and Functional Consequences of PLT Binding to Monocytes and Its Association with Clinical Features in SLE. Int J Mol Sci. 2021; 22(9). PMC: 8125177. DOI: 10.3390/ijms22094719. View

19.

Ferro D, Basili S, Alessandri C, Mantovani B, Cordova C, Violi F . Simvastatin reduces monocyte-tissue-factor expression type IIa hypercholesterolaemia. Lancet. 1998; 350(9086):1222. DOI: 10.1016/S0140-6736(05)63452-6. View

20.

Tobin W, Kinsella J, Collins D, Coughlan T, ONeill D, Egan B . Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: first results from the TRinity AntiPlatelet responsiveness (TrAP) study. Br J Haematol. 2011; 152(5):640-7. DOI: 10.1111/j.1365-2141.2010.08539.x. View