Volume 157, April 2023, 106373Author links open overlay panelAbstract

Blood platelets are best known for their roles in hemostasis and thrombosis, but platelets also make important contributions to inflammation, immunity, and inflammatory resolution. Experiments involving depletion, genetic modification, and live imaging of platelets in animal models have increased our mechanistic understanding of platelet contributions to inflammation. In this minireview, we provide a critical overview of experimental techniques for manipulating and imaging platelets in inflammation models. We then highlight studies using innovative approaches to elucidate molecular mechanisms through which platelet subsets, platelet Fc gamma receptors, and pro-resolution platelet functions influence inflammatory responses. We also propose future technologies and research directions which might move us closer to harnessing of platelet functions for improved therapeutic modulation of inflammatory diseases.

Section snippetsIntroduction: complex contributions of platelets to inflammation and immunity

Blood platelets respond to trauma and inflammation by accumulating at sites of injury to help maintain hemostasis. Preservation of vascular barrier integrity is itself an essential component of host defense against infection, but a growing body of research indicates that platelets are much more than simple cell fragments that plug holes and occasionally dislodge to cause thrombosis.

Over the last two decades, with intensification in recent years, application of mouse genetic tools has greatly

The expanding toolbox for in vivo studies of platelet contributions to inflammation

How do we know how platelets respond to and influence complex inflammatory responses? Identification of causal roles for platelets in inflammation and the molecular mediators of these responses has been achieved through experimental depletion, reconstitution, and genetic modification of platelets predominately in mouse models of inflammation. Table 1 provides a critical overview of these experimental approaches. In addition to these in vivo methods, approaches to alter human platelets are also

Harnessing platelet heterogeneity for immune-modulatory platelet transfusion therapies

The circulating platelet pool is heterogenous at baseline and after activation (Blair and Frelinger, 2019), but determining in vivo functions of different platelet subsets has been limited by the difficulty of isolating platelet populations for downstream functional assays. Valet et al. (2022) recently overcame challenges in ascertaining the ontogeny and function of a platelet subset using fluorescent reporter mice in transplantation and transfusion experiments in a model of septic peritonitis.

Concluding remarks

Advances in molecular biology have provided a wealth of tools for interrogating the contribution of platelets to inflammatory responses in vivo. Translating research findings from these models into improved health outcomes will require careful dissection of the roles of various platelet subsets across the complete time course of inflammatory responses in models designed to reflect human immune systems. In Table 3 we suggest potential future experimental approaches which could be useful for

Acknowledgements

Simon Cleary acknowledges salary support from a National Blood Foundation Early-Career Scientific Research Grant. Catharina Conrad is supported by an International Anesthesia Research Society Mentored Research Award. The authors declare no conflicts of interest.

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