Coronary artery disease, including myocardial infarction (MI), remains a leading cause of global mortality. Rapid reperfusion therapy is key to the improvement of patient outcome but contributes substantially to the final cardiac damage. This phenomenon is called “ischemia/reperfusion injury (IRI).” The underlying mechanisms of IRI are complex and not fully understood. Contributing cellular and molecular mechanisms involve the formation of microthrombi, alterations in ion concentrations, pH shifts, dysregulation of osmolality, and, importantly, inflammation. Beyond their known action as drivers of the development of coronary plaques leading to MI, platelets have been identified as important mediators in myocardial IRI. Circulating platelets are activated by the IRI-provoked damages in the vascular endothelium. This leads to platelet adherence to the reperfused endothelium, aggregation, and the formation of microthrombi. Furthermore, activated platelets release vasoconstrictive substances, act via surface molecules, and enhance leukocyte infiltration into post-IR tissue, that is, via platelet–leukocyte complexes. A better understanding of platelet contributions to myocardial IRI, including their interaction with other lesion-associated cells, is necessary to develop effective treatment strategies to prevent IRI and further improve the condition of the reperfused myocardium. In this review, we briefly summarize platelet properties that modulate IRI. We also describe the beneficial impacts of antiplatelet agents as well as their mechanisms of action in IRI beyond classic effects.

In addition to their essential role in hemostasis and thrombosis, platelets also modulate inflammatory reactions and immune responses. This is achieved by specialized surface receptors as well as secretory products including inflammatory mediators and cytokines. Platelets can support and facilitate the recruitment of leukocytes into inflamed tissue. The various properties of platelet function make it less surprising that circulating platelets are different within one individual. Platelets have different physical properties leading to distinct subtypes of platelets based either on their function (procoagulant, aggregatory, secretory) or their age (reticulated/immature, non-reticulated/mature). To understand the significance of platelet phenotypic variation, qualitatively distinguishable platelet phenotypes should be studied in a variety of physiological and pathological circumstances. The advancement in proteomics instrumentation and tools (such as mass spectrometry-driven approaches) improved the ability to perform studies beyond that of foundational work. Despite the wealth of knowledge around molecular processes in platelets, knowledge gaps in understanding platelet phenotypes in health and disease exist. In this review, we report an overview of the role of platelet subpopulations in inflammation and a selection of tools for investigating the role of platelet subpopulations in inflammation.

Reticulated platelets (RP) are the youngest platelet fraction released into the circulation. These immature platelets have increased RNA content, a larger cell volume, more dense granules, higher levels of surface activation markers and are thought to be more reactive compared to their mature counterparts. RP have been associated with cardiovascular disease, diabetes and increased mortality. Yet only a few animal studies investigating RP have been conducted so far and further investigations are warranted. Established methods to count RP are flow cytometry (staining with thiazole orange or SYTO13) or fully automated hematology analyzers (immature platelet fraction, IPF). IPF has been established as a diagnostic parameter in thrombocytopenia, cardiovascular disease and, in particular, the response to antiplatelet therapy. This review seeks to provide an overview of the key features of RP as well as preanalytical and analytical aspects that need to be considered when working with this platelet population.

Introduction: Serotonin is involved in leukocyte recruitment during inflammation. Deficiency of the serotonin transporter (SERT) is associated with metabolic changes in humans and mice. A possible link and interaction between the inflammatory effects of serotonin and metabolic derangements in SERT-deficient mice has not been investigated so far.Methods: SERT-deficient (Sert^-/-) and wild type (WT) mice were fed a high-fat diet, starting at 8 weeks of age. Metabolic phenotyping (metabolic caging, glucose and insulin tolerance testing, body and organ weight measurements, qPCR, histology) and assessment of adipose tissue inflammation (flow cytometry, histology, qPCR) were carried out at the end of the 19-week high-fat diet feeding period. In parallel, Sert^-/- and WT mice received a control diet and were analyzed either at the time point equivalent to high-fat diet feeding or as early as 8-11 weeks of age for baseline characterization.Results: After 19 weeks of high-fat diet, Sert^-/- and WT mice displayed similar whole-body and fat pad weights despite increased relative weight gain due to lower starting body weight in Sert^-/-. In obese Sert^-/- animals insulin resistance and liver steatosis were enhanced as compared to WT animals. Leukocyte accumulation and mRNA expression of cytokine signaling mediators were increased in epididymal adipose tissue of obese Sert^-/- mice. These effects were associated with higher adipose tissue mRNA expression of the chemokine monocyte chemoattractant protein 1 and presence of monocytosis in blood with an increased proportion of pro-inflammatory Ly6C+ monocytes. By contrast, Sert^-/- mice fed a control diet did not display adipose tissue inflammation.Discussion: Our observations suggest that SERT deficiency in mice is associated with inflammatory processes that manifest as increased adipose tissue inflammation upon chronic high-fat diet feeding due to enhanced leukocyte recruitment.

Background: Chronic urticaria is a skin disease with an important immunologic profile. There is a great interest not only due to its special clinical manifestation, but also due to its pathogenic mechanism. New data support the participation of ILs (interleukins) in the pathophysiology of CU (chronic urticaria). The aim of this study is to explore the change and its significance of cytokines, comparative characteristics of immune response - Th1/Th2 cytokines profiles balance in patients with CU in relation to atopy. Method: This prospective study included 46 patients with CU and 12 patients without urticaria or angioedema as a control group. Patients diagnosed with CU were separated to two subgroups with and without atopy (14/32). These patients were randomly selected at the Center of Asthma, Allergy and Clinical Immunology at TSMU. In peripheral blood was detected T CD4+, CD8+lymphocytes by flow cytometry using Becton Dikinson's monoclonal antibodies. The serum levels of IgE (total), sIL-2R, IL-6, IFN-γ, TNF-α, IL-4, IL-5, IL10, IL-13 were measured using ELISA, R&D System kits, Germany, at the lab of Immunology and Microbiology at TSU. Results: The concentrations of sIL-2R, IL-6, TNF-α, IFN-γ in CU patients were significantly higher than in control group (p=0.01). sIL-2R, IL-6, TNF-α concentrations in the atopic patients were higher than those in the CU patients without atopy (p<0.05). IFN-γ levels did not differ depending on the presence of atopy (p=0.9). IL-4, IL-5, IL10, IL-13 levels were higher in subjects with a history of angioedema (18.6pg/ml(1;31.7) compared with those without this condition (0pg/ml(0;22.6). This difference was statistically significant (Mann-Whitney test, p=0.01). Cytokine levels that have been studied correlated with each other as it follows – IFN-γ levels correlated with IL-10 and IL-13 levels (p=0.05), IL5-levels correlated with IL-6 levels (p<0.001), and other statistically significant correlations between the eight cytokines have not been observed in patients with CU. Conclusion: According our study was shown that chronic urticaria is not specifically characterized only by increasing level of Th1 or Th2 profile cytokines. There is a combination of mixed Th1/Th2. Not all patients with CU have the same profile of ILs. There was a dominant Th1 response in CU patients without atopy. Total Ig E level and certain etiological factors relatively specifically modulate the immune response of CU.