The dual role of platelet‐innate immune cell interactions in thrombo‐inflammation

Abstract

Beyond their role in hemostasis and thrombosis, platelets are increasingly recognized as key regulators of the inflammatory response under sterile and infectious conditions. Both platelet receptors and secretion are critical for these functions and contribute to their interaction with the endothelium and innate immune system. Platelet-leukocyte interactions are increased in thrombo-inflammatory diseases and are sensitive biomarkers for platelet activation and targets for the development of new therapies. The crosstalk between platelets and innate immune cells promotes thrombosis, inflammation, and tissue damage. However, recent studies have shown that these interactions also regulate the resolution of inflammation, tissue repair, and wound healing. Many of the platelet and leukocyte receptors involved in these bidirectional interactions are not selective for a subset of immune cells. However, specific heterotypic interactions occur in different vascular beds and inflammatory conditions, raising the possibility of disease-and organ-specific pathways of intervention. In this review, we highlight and discuss prominent and emerging interrelationships between platelets and innate immune cells and their dual role in the regulation of the inflammatory response in sterile and infectious thrombo-inflammatory diseases. A better understanding of the functional relevance of these interactions in different vascular beds may provide opportunities for successful therapeutic interventions to regulate the development, progression, and chronicity of various pathological processes. K E Y W O R D S immune cells, inflammation, platelets, thrombo-inflammation, thrombosis Essentials • Platelet-innate immune cell interactions regulate the development and outcome of thrombo-inflammatory diseases • Platelet activation potentiates innate immune cell recruitment, activation, and transmigration • Platelets promote the progression and resolution of inflammation in a disease-specific manner • Platelet-leukocyte interactions differentially regulate thrombo-inflammation Handling Editor: Cihan Ay JR, JHB AB, and SPW wrote the manuscript. ORCID Julie Rayes

Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with coronavirus disease‐19

“…PLT exists in an inactive form and can be activated quickly at the site of vascular injury, and can be rapidly activated in response to proinflammatory cytokine or infectious factors. The activation of platelets by this mechanism, even without any vascular damage, opens up new functions of platelets, namely inflammation and immune regulation, and the proinflammatory cytokine activity of PLT is mediated by its interaction with other leukocytes in the circulation, followed by the release of cytokines and chemokine to promote inflammation 29. Lymphocytes are the main immune-active cells in the human body, and lymphocyte count is an early marker of physiological stress and systemic inflammation.…”

Dysregulated primary hemostasis in critically ill COVID-19 patients

“…PPBP and SELPLG gene expression could also predict clinical outcome. Pro-platelet basic protein (PPBP), also known as CXCL7, is the most abundant platelet chemokine and (22,26) expressed within platelets as an inactive precursor and activated after cleavage during thrombus formation by enzymes released by neutrophils, while PSGL-1 is expressed by leukocytes, allowing the formation of platelet-leukocyte conjugates and adhesion of leukocytes to activated endothelium through its interaction with P-or E-selectin (22,27). PBPP has been shown to be essential for neutrophil migration into the thrombus (28) and the formation of plateletneutrophils aggregates (18), since its receptor, CXC chemokine receptor 2 (CXCR2), is expressed on the surface of neutrophil.…”

“…Finally, GP1BB encodes glycoprotein Ib, the receptor for vWF, and mediates platelet adhesion in the arterial circulation (23,33). Altogether, these upregulated genes recapitulate multiple steps of platelet activation (22,23).…”

“…Hierarchical clustering identi ed genes that were upregulated in a grade-dependent manner, thereby driving the hemostasis signature in critically ill patients (Figure 2b). These genes included ITG2AB, GP1BB, PPBP and SELPLG (Figure 3a), which recapitulated multiple steps of platelet activation (22,23). Importantly, and similarly to sP-selectin, RNA levels more strongly correlated with CRP level (Figure 3b) than with platelet counts (Figure 3c).…”

Observation of granulocyte function during ex vivo thrombus formation for patients with ANKRD26-associated thrombocytopenia

“…Отсутствие различий в морфологии лейкоцитов, а также данных о нарушении их функции затрудняет определение механизмов влияния мутации гена ANKRD26 на нарушение функции этих клеток [7,9] В связи с возрастающим количеством данных о двунаправленном влиянии гранулоцитов и тромбоцитов в различных патологических процессах, таких как атеросклероз, тромбоз глубоких вен, сепсис и др. [10], изучение функции обоих типов клеток при нарушениях в системах гемостаза и иммунитета представляет особый интерес. На данный момент клинических тестов для изучения влияния гранулоцитов на тромбообразование и, наоборот, степени активации тромбоцитов на активность лейкоцитов не существует.…”