Nature of Myeloid Cells Expressing Arginase 1 in Peripheral Blood After Trauma

Bryk, Jodie; Popović, Petar; Zenati, Mazen S.; Munera, Veronica; Pribis, John P.; Ochoa, Juan B.

doi:10.1097/ta.0b013e3181b026e4

Cited by 35 publications

(50 citation statements)

References 31 publications

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“…The results of this analysis are given approximately zero potentially subject to some granulocyte contamination in the isolation process. 33 Our findings, which demonstrated a minimal predicted percentage of granulocytes across the target study samples (1%; mean across study samples) illustrate the specificity of CP and are even more noteworthy when considering that granulocytes typically comprise the vast majority of white blood cell types (50% -70%) in the whole-blood of non-diseased individuals. As our target methylation data set consisted of technical replicate samples for five subjects, we were also interested in investigating the reproducibility of CP by comparing the predicted cell type proportions within a replicate pair.…”

Section: Resultsmentioning

confidence: 91%

Blood-based profiles of DNA methylation predict the underlying distribution of cell types

et al. 2013

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Section: Resultsmentioning

confidence: 91%

Blood-based profiles of DNA methylation predict the underlying distribution of cell types

et al. 2013

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“…A polarization of CD4 lymphocyte subsets away from Th1 and towards Th2 is known to occur early after severe injury and has been proposed to contribute to impaired immune defenses [13,14,48,65]. Increased numbers of MDSCs also appear in trauma patients [66,67], and both Th2 cells and MDSCs can produce type 2 cytokines [15,63,64]. ILC2, while rare, are robust producers of type 2 cytokines, particularly IL5 [59,68].…”

Section: Discussionmentioning

confidence: 99%

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

Guardado

Hoffman

et al. 2017

PLoS Med

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BackgroundThe immunosuppression and immune dysregulation that follows severe injury includes type 2 immune responses manifested by elevations in interleukin (IL) 4, IL5, and IL13 early after injury. We hypothesized that IL33, an alarmin released early after tissue injury and a known regulator of type 2 immunity, contributes to the early type 2 immune responses after systemic injury.Methods and findingsBlunt trauma patients admitted to the trauma intensive care unit of a level I trauma center were enrolled in an observational study that included frequent blood sampling. Dynamic changes in IL33 and soluble suppression of tumorigenicity 2 (sST2) levels were measured in the plasma and correlated with levels of the type 2 cytokines and nosocomial infection. Based on the observations in humans, mechanistic experiments were designed in a mouse model of resuscitated hemorrhagic shock and tissue trauma (HS/T). These experiments utilized wild-type C57BL/6 mice, IL33-/- mice, B6.C3(Cg)-Rorasg/sg mice deficient in group 2 innate lymphoid cells (ILC2), and C57BL/6 wild-type mice treated with anti-IL5 antibody.Severely injured human blunt trauma patients (n = 472, average injury severity score [ISS] = 20.2) exhibited elevations in plasma IL33 levels upon admission and over time that correlated positively with increases in IL4, IL5, and IL13 (P < 0.0001). sST2 levels also increased after injury but in a delayed manner compared with IL33. The increases in IL33 and sST2 were significantly greater in patients that developed nosocomial infection and organ dysfunction than similarly injured patients that did not (P < 0.05). Mechanistic studies were carried out in a mouse model of HS/T that recapitulated the early increase in IL33 and delayed increase in sST2 in the plasma (P < 0.005). These studies identified a pathway where IL33 induces ILC2 activation in the lung within hours of HS/T. ILC2 IL5 up-regulation induces further IL5 expression by CXCR2+ lung neutrophils, culminating in early lung injury. The major limitations of this study are the descriptive nature of the human study component and the impact of the potential differences between human and mouse immune responses to polytrauma. Also, the studies performed did not permit us to make conclusions about the impact of IL33 on pulmonary function.ConclusionsThese results suggest that IL33 may initiate early detrimental type 2 immune responses after trauma through ILC2 regulation of neutrophil IL5 production. This IL33–ILC2–IL5–neutrophil axis defines a novel regulatory role for ILC2 in acute lung injury that could be targeted in trauma patients prone to early lung dysfunction.

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“…Possibly, the produced IL-10, but also CD163 and arginase in adipose tissue macrophages only play a paracrine role, thereby preventing adipose tissue injury from excess inflammation and insulin resistance. Remarkably, circulating mononuclear cells from critically ill patients also appear to be switched to the M2-phenotype [20,21]. …”

Section: Discussionmentioning

confidence: 99%

Critical illness induces alternative activation of M2 macrophages in adipose tissue

et al. 2011

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IntroductionWe recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown.MethodsWe studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients.ResultsSubcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels.ConclusionsUnlike obesity, critical illness evokes adipose tissue accumulation of alternatively activated M2 macrophages, which have local anti-inflammatory and insulin sensitizing features. This M2 macrophage accumulation may contribute to the previously observed protective metabolic activity of adipose tissue during critical illness.

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Nature of Myeloid Cells Expressing Arginase 1 in Peripheral Blood After Trauma

Abstract: In humans, increased arginase 1 expression after trauma observed in the PBMC layer seems to be exclusively the result of an increased number of activated granulocytes.

Cited by 35 publications

References 31 publications

Blood-based profiles of DNA methylation predict the underlying distribution of cell types

Blood-based profiles of DNA methylation predict the underlying distribution of cell types

IL33-mediated ILC2 activation and neutrophil IL5 production in the lung response after severe trauma: A reverse translation study from a human cohort to a mouse trauma model

Critical illness induces alternative activation of M2 macrophages in adipose tissue

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