Nowadays, platelets are not only recognized for their central role in hemostasis and thrombosis but they are also increasingly considered as potent regulators of inflammation (Citation1). Indeed, there is mounting evidence that platelets contribute to the regulation of key steps of inflammatory and innate immune responses, including edema formation and leukocyte recruitment and activation. In addition, platelets can directly sense pathogens and endogenous danger signals, and promote the formation of antimicrobial and procoagulant neutrophil extracellular traps (NETs), through the expression of toll-like receptors (TLRs). Remarkably, at the same time platelets help leukocytes to infiltrate tissues and exert their immune functions, they limit host tissue collateral damage by repairing vascular breaches caused by leukocyte trafficking and activation (Citation2). Thus, with respect to tissue homeostasis and integrity, platelets exert both protective and potentially tissue-damaging activities in inflamed organs, which illustrate the duality of platelets in inflammation.
Due to the ever-growing diversity of functions attributed to platelets in a wide variety of inflammatory diseases and models, it is impossible to get a full picture of the roles of platelets in inflammation. Nevertheless, this review series aims to give the readers of Platelets a non-exhaustive overview that stresses both the multifaceted nature and importance of platelet inflammatory and immune functions.
The discovery by several groups in 2005 (Citation3–Citation5) that platelets express TLRs has provided a strong evidence for a link between hemostasis and innate immunity and stimulated research on the immune functions and properties of platelets. In the first review of this series, Hamzeh-Cognasse et al., who were part of the pioneer groups that described TLRs on human platelets, present and integrate recent progress on TLR-mediated platelet signaling and functions.
The participation of platelets in inflammation does not solely rely on their membrane receptors, but also involves secretion of their granule content. The involvement of platelet granule content in the immunomodulatory functions of platelets is highlighted in the review by Mammadova Bach et al on platelet serotonin. Platelet serotonin, which represents the majority of peripheral serotonin, is mostly known for its vasoconstrictive properties (Citation6). Mammadova Bach et al. recalls us that the functions of peripheral serotonin go beyond the field of hemostasis, as serotonin also influences a variety of inflammatory processes through autocrine and paracrine engagement of different receptors expressed in various organs and cells.
The review by Carsten Deppermann describes how platelets prevent bleeding in inflamed organs, with a special emphasis on the role of both platelet adhesion receptors and of platelet granule secretion in this function, and on its context- and organ-dependent aspects.
Olsson and Cedervall discuss the pro-inflammatory roles of platelets in the context of cancer, which notably involve tight interactions with neutrophils and participation in NETs formation, and, more generally, regulation of cancer-associated inflammation and thrombosis.
Finally, although the healing properties of platelets have long been known and taken advantage of in clinics to improve tissue regeneration, data on the role of platelets in inflammation resolution and post-inflammation healing are scarce. In the last review of this series, Julia Etulain presents the effect of platelet-derived growth factors and cytokines in wound healing, whose different phases include acute inflammation and resolution of inflammation, and discusses current and future prospects for the use of platelet-rich plasma in regenerative medicine.
There are still many gaps in our knowledge on the roles of platelets in inflammation and immune responses and much research remains to be done. Nonetheless, as highlighted in several articles of this review series, the fact that platelets intervene in those processes has opened the exciting perspective of exploiting the vast repertoire of antiplatelet medications for treatment of diseases with an inflammatory component.
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References
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