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Cells
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Role of Platelets in Inflammatory Diseases
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Role of Platelets in Inflammatory Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 January 2022) | Viewed by 50107

Special Issue Editor

Dr. Zhenyu Li

E-Mail Website
Guest Editor
Department of Medicine and Molecular & Cellular Biochemistry, College of Medicine, University of Kentucky, 741 South Limestone Street, Lexington, KY 40536, USA
Interests: cellular signaling; platelet; endothelial cell; vascular permeability; inflammation; thrombosis; extracellular vesicles; sepsis

Special Issue Information

Dear Colleagues,

Platelets are a central player at the interface between thrombosis and inflammation. During inflammatory and infectious diseases, platelets physically interact with circulating leukocytes and regulate leukocyte function. Neutrophil–platelet interaction drives the formation of neutrophil extracellular traps (NETs). Activated platelets release soluble mediators into circulation that may have local and systemic effects on leukocytes and vascular cells. Platelet-derived microvesicles may contribute to coagulation, inflammation, and infection. Platelets can also interact with a wide variety of microbial pathogens and may play an important role in the clearance of pathogens. Emerging evidence suggests that platelets may participate in a wide variety of processes involving tissue injury, immune responses, and repair that underlie diverse diseases such as atherosclerosis, autoimmune disorders, inflammatory disorders, host-defense responses, and sepsis.

However, we are still far from fully understanding the molecular mechanisms by which platelets participate in inflammatory diseases. For instance, platelets have been shown to either promote or inhibit macrophage functions. These contrary findings undoubtedly reflect the large variety of molecular and cellular processes regulated by platelets. This Special Issue will summarize the latest molecular and cellular mechanisms involved in the role of platelets in inflammatory and infectious diseases. Potential therapies by targeting platelet function to prevent or treat the progression of these diseases will also be addressed.

We look forward to your contributions.

Dr. Zhenyu Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • platelet
  • thrombosis
  • inflammation
  • thrombocytopenia
  • extracellular vesicles
  • sepsis
  • secretion
  • coagulation
  • vascular permeability
  • therapeutic targets

Published Papers (6 papers)

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Research

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12 pages, 1843 KiB  
Article
Platelet Aggregation, Mitochondrial Function and Morphology in Cold Storage: Impact of Resveratrol and Cytochrome c Supplementation
by Michael L. Ekaney, Juan Carlos Carrillo-Garcia, Gabrielle Gonzalez-Gray, Hadley H. Wilson, Mary M. Jordan, Iain H. McKillop and Susan L. Evans
Cells 2023, 12(1), 166; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12010166 - 30 Dec 2022
Cited by 4 | Viewed by 1474
Abstract
Donated platelets are critical components of hemostasis management. Extending platelet storage beyond the recommended guidelines (5 days, 22 °C) is of clinical significance. Platelet coagulation function can be prolonged with resveratrol (Res) or cytochrome c (Cyt c) at 4 °C. We hypothesized that [...] Read more.
Donated platelets are critical components of hemostasis management. Extending platelet storage beyond the recommended guidelines (5 days, 22 °C) is of clinical significance. Platelet coagulation function can be prolonged with resveratrol (Res) or cytochrome c (Cyt c) at 4 °C. We hypothesized that storage under these conditions is associated with maintained aggregation function, decreased reactive oxygen species (ROS) production, increased mitochondrial respiratory function, and preserved morphology. Donated platelets were stored at 22 °C or 4 °C supplemented with 50 μM Res or 100 μM Cyt c and assayed on days 0 (baseline), 5, 7 and 10 for platelet aggregation, morphology, intracellular ROS, and mitochondrial function. Declining platelet function and increased intracellular ROS were maintained by Res and Cyt c. Platelet respiratory control ratio declined during storage using complex I + II (CI + CII) or CIV substrates. No temperature-dependent differences (4 °C versus 22 °C) in respiratory function were observed. Altered platelet morphology was observed after 7 days at 22 °C, effects that were blunted at 4 °C independent of exposure to Res or Cyt c. Storage of platelets at 4 °C with Res and Cyt c modulates ROS generation and platelet structural integrity. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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9 pages, 943 KiB  
Article
Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome
by William T. Gunning, Paula M. Kramer, Jacob A. Cichocki, Beverly L. Karabin, Sadik A. Khuder and Blair P. Grubb
Cells 2022, 11(5), 774; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11050774 - 23 Feb 2022
Cited by 8 | Viewed by 30514
Abstract
A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies [...] Read more.
A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease. In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated. This case–control study validates our pilot study results that POTS patients have an activated innate immune system. Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as “non-POTS” subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules. Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001. Of particular interest were elevations of IL-1β and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory. All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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Review

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25 pages, 21858 KiB  
Review
Role of Platelets in Osteoarthritis—Updated Systematic Review and Meta-Analysis on the Role of Platelet-Rich Plasma in Osteoarthritis
by Ewa Tramś, Kamila Malesa, Stanisław Pomianowski and Rafał Kamiński
Cells 2022, 11(7), 1080; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11071080 - 23 Mar 2022
Cited by 11 | Viewed by 5520
Abstract
Platelets are an essential component of hemostasis, with an increasing role in host inflammatory processes in injured tissues. The reaction between receptors and vascular endothelial cells results in the recruitment of platelets in the immune response pathway. The aim of the present review [...] Read more.
Platelets are an essential component of hemostasis, with an increasing role in host inflammatory processes in injured tissues. The reaction between receptors and vascular endothelial cells results in the recruitment of platelets in the immune response pathway. The aim of the present review is to describe the role of platelets in osteoarthritis. Platelets induce secretion of biological substances, many of which are key players in the inflammatory response in osteoarthritis. Molecules involved in cartilage degeneration, or being markers of inflammation in osteoarthritis, are cytokines, such as tumor necrosis factor α (TNFα), interleukins (IL), type II collagen, aggrecan, and metalloproteinases. Surprisingly, platelets may also be used as a treatment modality for osteoarthritis. Multiple randomized controlled trials included in our systematic review and meta-analyses prove the effectiveness of platelet-rich plasma (PRP) as a minimally invasive method of pain alleviation in osteoarthritis treatment. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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11 pages, 558 KiB  
Review
Platelets, a Key Cell in Inflammation and Atherosclerosis Progression
by Ricardo Huilcaman, Whitney Venturini, Lucia Fuenzalida, Angel Cayo, Raul Segovia, Claudio Valenzuela, Nelson Brown and Rodrigo Moore-Carrasco
Cells 2022, 11(6), 1014; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11061014 - 17 Mar 2022
Cited by 24 | Viewed by 3783
Abstract
Platelets play important roles in thrombosis-dependent obstructive cardiovascular diseases. In addition, it has now become evident that platelets also participate in the earliest stages of atherosclerosis, including the genesis of the atherosclerotic lesion. Moreover, while the link between platelet activity and hemostasis has [...] Read more.
Platelets play important roles in thrombosis-dependent obstructive cardiovascular diseases. In addition, it has now become evident that platelets also participate in the earliest stages of atherosclerosis, including the genesis of the atherosclerotic lesion. Moreover, while the link between platelet activity and hemostasis has been well established, the role of platelets as modulators of inflammation has only recently been recognized. Thus, through their secretory activities, platelets can chemically attract a diverse repertoire of cells to inflammatory foci. Although monocytes and lymphocytes act as key cells in the progression of an inflammatory event and play a central role in plaque formation and progression, there is also evidence that platelets can traverse the endothelium, and therefore be a direct mediator in the progression of atherosclerotic plaque. This review provides an overview of platelet interactions and regulation in atherosclerosis. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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16 pages, 833 KiB  
Review
The Underestimated Role of Platelets in Severe Infection a Narrative Review
by Alberto Fogagnolo, Gianluca Calogero Campo, Matilde Mari, Graziella Pompei, Rita Pavasini, Carlo Alberto Volta and Savino Spadaro
Cells 2022, 11(3), 424; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030424 - 26 Jan 2022
Cited by 9 | Viewed by 3880
Abstract
Beyond their role in hemostasis, platelets have emerged as key contributors in the immune response; accordingly, the occurrence of thrombocytopenia during sepsis/septic shock is a well-known risk factor of mortality and a marker of disease severity. Recently, some studies elucidated that the response [...] Read more.
Beyond their role in hemostasis, platelets have emerged as key contributors in the immune response; accordingly, the occurrence of thrombocytopenia during sepsis/septic shock is a well-known risk factor of mortality and a marker of disease severity. Recently, some studies elucidated that the response of platelets to infections goes beyond a simple fall in platelets count; indeed, sepsis-induced thrombocytopenia can be associated with—or even anticipated by—several changes, including an altered morphological pattern, receptor expression and aggregation. Of note, alterations in platelet function and morphology can occur even with a normal platelet count and can modify, depending on the nature of the pathogen, the pattern of host response and the severity of the infection. The purpose of this review is to give an overview on the pathophysiological interaction between platelets and pathogens, as well as the clinical consequences of platelet dysregulation. Furthermore, we try to clarify how understanding the nature of platelet dysregulation may help to optimize the therapeutic approach. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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15 pages, 1544 KiB  
Review
Platelet Function, Role in Thrombosis, Inflammation, and Consequences in Chronic Myeloproliferative Disorders
by Lisa Repsold and Anna Margaretha Joubert
Cells 2021, 10(11), 3034; https://doi.org/10.3390/cells10113034 - 5 Nov 2021
Cited by 31 | Viewed by 4024
Abstract
Platelets are conventionally defined as playing a vital role in homeostasis and thrombosis. This role has over the years transformed as knowledge regarding platelets has expanded to include inflammation, cancer progression, and metastasis. Upon platelet activation and subsequent aggregation, platelets release a host [...] Read more.
Platelets are conventionally defined as playing a vital role in homeostasis and thrombosis. This role has over the years transformed as knowledge regarding platelets has expanded to include inflammation, cancer progression, and metastasis. Upon platelet activation and subsequent aggregation, platelets release a host of various factors, including numerous pro-inflammatory factors. These pro-inflammatory factors are recruiters and activators of leukocytes, aiding in platelets’ immune regulating function and inflammatory function. These various platelet functions are interrelated; activation of the inflammatory function results in thrombosis and, moreover, in various disease conditions, can result in worsened or chronic pathogenesis, including cancer. The role and contribution of platelets in a multitude of pathophysiological events during hemostasis, thrombosis, inflammation, cancer progression, and metastasis is an important focus for ongoing research. Platelet activation as discussed here is present in all platelet functionalities and can result in a multitude of factors and signaling pathways being activated. The cross-talk between inflammation, cancer, and platelets is therefore an ideal target for research and treatment strategies through antiplatelet therapy. Despite the knowledge implicating platelets in these mentioned processes, there is, nevertheless, limited literature available on the involvement and impact of platelets in many diseases, including myeloproliferative neoplasms. The extensive role platelets play in the processes discussed here is irrefutable, yet we do not fully understand the complete interrelation and extent of these processes. Full article
(This article belongs to the Special Issue Role of Platelets in Inflammatory Diseases)
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