Platelet-monocyte interactions in Systemic Lupus Erythematosus
Final Report Abstract
I have shown that platelet:monocyte interaction shapes the monocyte transcriptome and phenotype in thromboinflammation. Consistent with a proinflammatory platelet effector role, MPA were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (p<0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30% and 21% reduction, p<0.05, respectively) and decreased monocyte CD40 and TF expression while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM. While the COVID-19 pandemic temporarily interrupted my main research project, the finding that infected patients developed a substantial risk of thromboembolic adverse events fueled additional scientific projects in which I critically contributed to analyzing the effector role of platelets on endothelial cells. Here, we could demonstrate that COVID-19 platelets are proinflammatory, exhibit upregulation of inflammatory pathways, and induce endothelial dysfunction.
Publications
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Platelets amplify endotheliopathy in COVID-19. Science Advances, 7(37).
Barrett, Tessa J.; Cornwell, MacIntosh; Myndzar, Khrystyna; Rolling, Christina C.; Xia, Yuhe; Drenkova, Kamelia; Biebuyck, Antoine; Fields, Alexander T.; Tawil, Michael; Luttrell-Williams, Elliot; Yuriditsky, Eugene; Smith, Grace; Cotzia, Paolo; Neal, Matthew D.; Kornblith, Lucy Z.; Pittaluga, Stefania; Rapkiewicz, Amy V.; Burgess, Hannah M.; Mohr, Ian; ... & Berger, Jeffrey S.
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Platelet‐conditioned media induces an anti‐inflammatory macrophage phenotype through EP4. Journal of Thrombosis and Haemostasis, 19(2), 562-573.
Heffron, Sean P.; Weinstock, Ada; Scolaro, Bianca; Chen, Shiyu; Sansbury, Brian E.; Marecki, Greg; Rolling, Christina C.; El, Bannoudi Hanane; Barrett, Tessa; Canary, James W.; Spite, Matthew; Berger, Jeffrey S. & Fisher, Edward A.
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P2Y12 Inhibition Suppresses Proinflammatory Platelet–Monocyte Interactions. Thrombosis and Haemostasis, 123(02), 231-244.
Barrett, Tessa J.; Berger, Jeffrey S.; Rolling, Christina C.; Sowa, Marcin A.; Wang, Tricia T.; Cornwell, MacIntosh; Myndzar, Khrystyna; Schwartz, Tamar; El, Bannoudi Hanane & Buyon, Jill
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Platelet LGALS3BP as a Mediator of Myeloid Inflammation in Systemic Lupus Erythematosus. Arthritis & Rheumatology, 75(5), 711-722.
El, Bannoudi Hanane; Cornwell, MacIntosh; Luttrell‐Williams, Elliot; Engel, Alexis; Rolling, Christina; Barrett, Tessa J.; Izmirly, Peter; Belmont, H. Michael; Ruggles, Kelly; Clancy, Robert; Buyon, Jill & Berger, Jeffrey S.
