Abstract
BackgroundAcute respiratory distress syndrome (ARDS) is a disease associated with a high mortality rate. The initial phase is characterized by induction of inflammatory cytokines and chemokines and influx of circulating inflammatory cells, including macrophages which play a pivotal role in the innate and adaptive immune responses to injury. Growing evidence points to phenotypic heterogeneity and plasticity between various macrophage activation states.MethodsIn this study, gene expression in alveolar macrophages and circulating leukocytes from healthy control subjects and patients with ARDS was assessed by mRNA microarray analysis.ResultsBoth alveolar macrophages and circulating leukocytes demonstrated up-regulation of genes encoding chemotactic factors, antimicrobial peptides, chemokine receptors, and matrix metalloproteinases. Two genes, the pro-inflammatory S100A12 and the anti-inflammatory IL-1 decoy receptor IL-1R2 were significantly induced in both cell populations in ARDS patients, which was confirmed by protein quantification. Although S100A12 levels did not correlate with disease severity, there was a significant association between early plasma levels of IL-1R2 and APACHE III scores at presentation. Moreover, higher levels of IL-1R2 in plasma were observed in non-survivors as compared to survivors at later stages of ARDS.ConclusionsThese results suggest a hybrid state of alveolar macrophage activation in ARDS, with features of both alternative activation and immune tolerance/deactivation.. Furthermore, we have identified a novel plasma biomarker candidate in ARDS that correlates with the severity of systemic illness and mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0190-x) contains supplementary material, which is available to authorized users.
Highlights
Acute respiratory distress syndrome (ARDS) is a deadly disease, with an incidence of roughly 200,000 cases per year in the United States and a mortality rate of approximately 40% [1]
Inflammatory gene expression is increased in alveolar macrophages of ARDS patients Microarray analysis was performed on AM isolated from bronchoalveolar lavage (BAL) fluid of patients with ARDS and controls
CD177, which was up-regulated in both the AM and in buffy coat cells of ARDS patients, is a molecule expressed by both activated neutrophils and macrophages that interacts with the Platelet endothelial cell adhesion molecule 1 (PECAM-1), indicating a role in leukocyte extravasation and transmigration into inflammatory environments [33]
Summary
Acute respiratory distress syndrome (ARDS) is a deadly disease, with an incidence of roughly 200,000 cases per year in the United States and a mortality rate of approximately 40% [1]. Macrophages play a pivotal role in the innate and adaptive immune responses during host defense and response to injury. Recent research has uncovered distinctly heterogeneous populations of macrophages, as well as plasticity between different macrophage phenotypes [6]. This phenotypic polarization of macrophages is believed to be a consequence of factors present within the cell’s. The initial phase is characterized by induction of inflammatory cytokines and chemokines and influx of circulating inflammatory cells, including macrophages which play a pivotal role in the innate and adaptive immune responses to injury. Growing evidence points to phenotypic heterogeneity and plasticity between various macrophage activation states
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
