Seminars in immunopathology
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The integrity of our bodies is under constant threat by external forces. Blood coagulation and inflammatory pathways are important, highly efficient defence systems that support health and well-being in both normal and challenged conditions. Being potentially dangerous for the own organism, they are kept under strict control by anticoagulant and anti-inflammatory mechanisms. ⋯ Efficient anticoagulant systems not only keep coagulation reactions under strict control but also exert control on inflammatory reactions. During inflammation, these anticoagulant/anti-inflammatory systems are repressed allowing full activation of coagulation and inflammation. Dysregulation of the delicate balance between these systems contributes to the pathogenesis of many diseases.
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Review
Microparticles: a critical component in the nexus between inflammation, immunity, and thrombosis.
Plasma membrane remodeling characterized by phosphatidylserine exposure and consecutive microparticle (MP) shedding is an ubiquitous process enabling the clearance of senescent cells and the maintenance of tissue homeostasis. MPs are released as fragments from the budding plasma membrane of virtually all eukaryotic cell types undergoing stimulation or apoptosis and may be considered a broad primitive response to stress. MP release is dependent on cytoskeleton degradation pathways involving caspases, requires a sustained increase in intracellular calcium triggering K+ and Cl- efflux and is possibly tuned by mitochondria permeability changes. ⋯ Because of their multiple properties that are characteristic of a private response of the parental cell, MPs could act as cytoprotective and anti-inflammatory agents through the delivery of activated protein C or annexin 1 and could contribute to the limitation of vascular hyporeactivity. Owing to their ability to cargo bioactive signals, MPs could be viewed as an integrated communication network enabling the coordination of complex cellular responses in biological fluids and the maintenance of the homeostasis equation. A better understanding of the molecular mechanisms involved in MP shedding would pave the way of a new pharmacological approach aiming at the control of MP-driven cellular responses.
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Lung transplantation is a viable treatment option for select patients with end-stage lung disease. Two issues hamper progress in transplantation: first, donor shortage is a major limitation to increasing the number of transplants performed. Secondly, recipient outcomes remain disappointing when compared with other solid organ transplant results. ⋯ PGD is the culmination of a series of insults, hemodynamic, metabolic, and inflammatory, that begin with the brain dead donor and result in poor recipient outcomes. Understanding the mechanism of donor lung injury resulting from brain death and the possible treatment strategies for its inhibition could help to increase the number of usable lungs and decrease the rate of PGD in the recipient. Here we present a review of the key pathways which result in donor lung injury, and follow this with a brief review of recent biomarkers that are proving to be instrumental to our ability to predict truly unsuitable lungs, and our ability to predict and hopefully prevent or treat recipients with subsequent lung injury.
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Mammals coexist with an extremely dense microbiota in the lower intestine. Despite the constant challenge of small numbers of microbes penetrating the intestinal surface epithelium, it is very unusual for these organisms to cause disease. In this review article, we present the different mucosal firewalls that contain and allow mutualism with the intestinal microbiota.
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Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder leading to cardiovascular and metabolic complications. OSA is also a multicomponent disorder, with intermittent hypoxia (IH) as the main trigger for the associated cardiovascular and metabolic alterations. Indeed, recurrent pharyngeal collapses during sleep lead to repetitive sequences of hypoxia-reoxygenation. ⋯ Oxidative stress, inflammation, and vascular remodeling can be directly triggered by IH, further aggravated by the OSA-associated hormonometabolic alterations, such as insulin resistance, dyslipidemia, and adipokine imbalance. As shown in OSA patients and in the animal model, genetic susceptibility, comorbidities (obesity), and life habits (high fat diet) may aggravate atherosclerosis development or progression. The intimate molecular mechanisms are still largely unknown, and their understanding may contribute to delineate new targets for prevention strategies and/or development of new treatment of OSA-related atherosclerosis, especially in patients at risk for cardiovascular disease.