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Extracellular vesicles (EVs) in the plasma mediate important intercellular communications in the pathogenesis of cancer and inflammatory diseases. EVs express integrins that regulate target specificities and programmed cell death ligand 1 and 2 (PD-L1 and 2) that suppress lymphocyte activation. However, the roles of these molecules on EVs in systemic inflammatory response syndrome (SIRS) and sepsis remain little understood. This study aimed to investigate how the EV expression of integrins and PD-1 ligands might differ in SIRS and sepsis, compared with healthy controls, and to correlate their expression with the clinical parameters reflecting pathogenesis. Twenty-seven SIRS patients without sepsis, 27 sepsis patients, and 18 healthy volunteers were included. EVs were isolated from plasma samples. The expression of three major integrins (β1, β2, β3 integrins) and PD-L1 and 2 were measured. The EV expression of β2 integrin and PD-L2 was significantly increased in sepsis patients compared with healthy controls. EV expression of PD-L1 was not elevated in sepsis and SIRS; however, circulating soluble PD-L1 levels were significantly higher in sepsis. Furthermore, EV expression of β2 integrin in sepsis patients correlated with hypotension and reduced kidney function. In addition, soluble PD-L1 levels correlated with sepsis severity, impaired kidney function, and impaired central nervous system function. These results suggest the potential involvements of the EV β2 integrin, as well as EV PD-L2 and soluble PD-L1, in the septic pathogenesis that occurs with the systemic immune activation leading to multiple organ dysfunctions.

Introduction: Adhesive molecules, particularly selectins and integrins, are critical for the inflammatory cell trafficking from blood to the lungs. Among integrins, the most important for cell infiltration are those containing α₄ and β₂ subunits., Objectives: The aim of this study was to evaluate the expression of α₁ and α₂ integrin subunits on peripheral blood T cells in asthmatic subjects, because previously we showed evidence that α₁β₁ and α₂β₁ integrins may be found on peripheral blood eosinophils in these subjects. In this study, we also analyzed the expression of α₄ and β₁ subunits as a positive reference., Patients and Methods: Expression of α₁, α₂, α₄, and β₁ subunits was analyzed by flow cytometry on CD₄+ and CD8+ T lymphocytes obtained from the peripheral blood of 54 clinically stable, asymptomatic, mild-to-moderate persistent asthmatics and 40 healthy controls., Results: The α₁ subunit was not present on peripheral blood T cells in the majority of subjects in both study groups. Expression of α₂ was detectable on CD8+ cells in both groups and was increased on CD4+ in asthmatics. Both types of T cells showed higher expression of α₄ and β₁ in patients with asthma. Expression of α₄ was higher on CD8+ T cells both in asthmatics and controls., Conclusions: Expression of α₄ and β₁ integrin subunits is increased on peripheral blood T cells in patients with asthma, which confirms the preactivation of blood lymphocytes even in stable and asymptomatic disease. The biological role of α₂ subunit on T cells remains to be elucidated.

Migration of neutrophils requires sequential adhesive and deadhesive interactions between beta 1 and beta 2 integrins and components of the extracellular matrix. Prompted by reports that describe interaction of soluble beta-glucan with the beta 2 integrin Mac-1, a role for beta-glucan in regulation of integrin-mediated migration was investigated. Neutrophil migration in response to fMLP was assessed using an agarose overlay method with slides precoated with fibronectin (Fn) +/- beta-glucan. On Fn, random migration in excess of directed migration was observed. In contrast, migration on Fn + beta-glucan was directional, with marked diminution of random migration. This conversion of random to directed migration was seen neither when Fn was supplemented with alternative polysaccharides nor when beta-glucan was applied to other components of the extracellular matrix. This effect of beta-glucan was shown to be cation dependent and to be effected by Arg-Gly-Asp-containing peptides consistent with an integrin-mediated event. mAb inhibition studies demonstrate that beta-glucan effects this shift toward directed migration through suppression of migration mediated by Mac-1 and very late Ag 5 and enhancement of very late Ag 3-mediated migration. Adhesion assays suggest that the prochemotactic influence of beta-glucan is due, in part but not entirely, to modulation of PMN adhesion to Fn. In summary, these data support a novel role for beta-glucan in regulation of beta 1- and beta 2-mediated neutrophil migration on Fn.