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Endothelial cells have a crucial role in several physiologic processes: blood fluidity, vasomotor tone regulation, osmotic balance, and vascular barrier function.
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Sepsis, a state of systemic inflammation, induces endothelial cell activation but can lead to endothelial dysfunction and multiorgan failure.
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The endothelium has a key role in organizing the innate immune response during sepsis, but it also exhibits properties involved in the activation of adaptive immunity.
Immune Consequences of Endothelial Cells’ Activation and Dysfunction During Sepsis
Section snippets
Key points
Resting endothelial cells
In basal conditions, vascular ECs display transport and permeability functions, and maintain and regulate blood flow. All these fundamental homeostatic functions have already been reviewed in depth elsewhere.10, 11, 12, 13
In brief, the endothelium plays a crucial role in homeostasis. Based on structural aspects, ECs express tight junctions, adherens junctions, and gap junctions.14, 15, 16 Intercellular junctions can dynamically change and allow the passage of cellular elements, fluid, and
Role of endothelial cells in innate immunity
Sepsis, as well as other diseases, induces acute systemic inflammation but overall can lead to homeostasis dysregulation by the loss or inappropriate exaggeration of ECs functions. Acute inflammation induces “endothelial cell activation,” defined as the acquisition of new properties by resting ECs.10 Different stimuli that are released into the blood circulation, such as PAMPs (ie, lipopolysaccharide [LPS]) or proinflammatory cytokines, may activate ECs and provoke proinflammatory responses.38
Role of endothelial cells in adaptive immunity
ECs may also participate in the activation of adaptive immunity via several pathways. As already mentioned, ECs, like dendritic cells, are reported to express both TLRs and NLRs. Muramyl dipeptide, a bacterial component, is recognized by NLR-2 in ECs, leading to the upregulation of IL-6 secretion, which induces CD4+ T helper cell (Th)17 polarization and inhibits CD4+ Th1 and Th2 responses.72 Moreover, platelet-EC interactions may participate in adaptive immunity activation. Indeed, platelets
Endothelial cell heterogeneity and organ dysfunction during sepsis
The endothelium plays a central role in the pathogenesis of sepsis leading to multiorgan failure syndrome. The endothelium is highly heterogeneous in morphology and function between different organs, and between different vessels in the same organ. For example, during sepsis, the procoagulant properties of ECs are differentially regulated between vascular beds. Yamamoto and Loskutoff94 showed that LPS infusion may result in organ-specific deposition of fibrin in the kidney and adrenal gland. In
Summary
The endothelium has a fundamental role in many essential physiologic functions. Its heterogeneity in morphology and function explains that its roles can vary from one organ to another or according to the type of vessel. Moreover, owing to their localization, ECs are one of the first cells able to detect circulating pathogens and can initiate a powerful proinflammatory response as well as the recruitment and trafficking of innate immune cells. ECs may also participate in the activation of
Disclosure
S. Pons received a research grant from the French Intensive Care Society and one from the European Society of Intensive Care Medicine. L. Zafrani and M. Arnaud received a research grant from Jazz Pharma. E. Arrii has received fees for lectures from MSD, Pfizer, and Alexion. Her institution and research group have received support from Baxter, Jazz Pharma, Fisher & Payckle, Gilead, Alexion, and Ablynx. The remaining authors have disclosed that they do not have any conflicts of interest.
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