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CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites
Katharine M. Irvine, … , Matthew J. Sweet, Elizabeth E. Powell
Katharine M. Irvine, … , Matthew J. Sweet, Elizabeth E. Powell
Published June 2, 2016
Citation Information: JCI Insight. 2016;1(8):e86914. https://doi.org/10.1172/jci.insight.86914.
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Research Article Hepatology Inflammation

CRIg-expressing peritoneal macrophages are associated with disease severity in patients with cirrhosis and ascites

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Abstract

Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIghi macrophages differed between patients and in the same patient over time, and a high proportion of CRIghi macrophages was associated with reduced disease severity (model for end-stage liver disease) score. As compared with CRIglo macrophages, CRIghi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities among CRIghi cells, human macrophages, and mouse F4/80hi resident peritoneal macrophages and among CRIglo macrophages, human monocytes, and mouse F4/80lo monocyte-derived peritoneal macrophages. These data suggest that CRIghi and CRIglo macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable among patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.

Authors

Katharine M. Irvine, Xuan Banh, Victoria L. Gadd, Kyle K. Wojcik, Juliana K. Ariffin, Sara Jose, Samuel Lukowski, Gregory J. Baillie, Matthew J. Sweet, Elizabeth E. Powell

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Figure 4

Increased phagocytic capacity for latex beads in CRIghi macrophages.

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Increased phagocytic capacity for latex beads in CRIghi macrophages.
Rep...
Representative histograms showing CCR2+ (CRIglo) and CCR2– (CRIghi) uptake of (A) unopsonized and (B) IgG-opsonized FitC-labeled latex beads in the absence or presence of 10 μg/ml Cytochalasin D. (C) Latex bead binding and (D) internalization capacity in CCR2+ (CRIglo) and CCR2– (CRIghi) macrophages (n = 3, multiple t tests [CCR2+ vs. CCR2–] and repeated-measures 2-way ANOVA [serum vs. HI serum], data represent mean ± SEM). HI, heat inactivated.

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