• The Journal of infection · Nov 2012

    Gene expression profiling reveals the defining features of monocytes from septic patients with compensatory anti-inflammatory response syndrome.

    • Ping-bo Xu, Jing-Sheng Lou, Yu Ren, Chang-Hong Miao, and Xiao-ming Deng.
    • Department of Anesthesiology, Fudan University Shanghai Cancer Center, No. 270, Dong an Road, Shanghai 200032, PR China.
    • J. Infect. 2012 Nov 1; 65 (5): 380-91.

    ObjectivesTo characterize the expression profiles of genes in purified monocytes from septic patients during systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS), and then to investigate the potential mechanism of monocyte deactivation.MethodsLipopolysaccharides (LPS)-induced cytokine responses, phagocytosis assay and migration assay were performed in monocytes from SIRS patients, CARS patients and healthy volunteers (n = 8). After functional assays, each pair of samples from the same group was pooled into one for gene expression analysis. All new samples (n = 4) were hybridized on NimbleGen human gene expression 12 × 135 K microarrays, and selected genes were validated by real-time polymerase chain reaction. Pathway analysis and Gene Ontology analysis were performed on differentially expressed genes using Agilent GeneSpring (version 11.0).ResultsA set of genes related to pro-inflammation, phagocytosis, chemotaxis, antigen presentation, and anti-apoptosis were significantly down-regulated, while some genes associated with pro-apoptosis and anti-inflammation were up-regulated instead on monocytes from CARS patients compared with SIRS patients and healthy volunteers. Monocytes from CARS patients showed impaired production of TNF-α and IL-6, and increased release of IL-10 when stimulated by LPS. Functional analysis confirmed reduced phagocytosis and migratory activity of monocytes from CARS patients. Human leukocyte antigen-DR (HLA-DR) measurements demonstrated decreased expression of HLA-DR on monocytes from CARS patients.ConclusionMonocytes from CARS patients exhibited significant changes in mRNA expression of genes associated with phagocytosis, antigen presentation, inflammatory response, cell migration, and apoptosis, which might cause deactivation of monocytes during CARS.Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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