Differential in vivo activation of monocyte subsets during low-grade inflammation through experimental endotoxemia in humans

Thaler, Barbara; Hohensinner, Philipp J.; Krychtiuk, Konstantin A.; Matzneller, Peter; Koller, Lorenz; Brekalo, Mira; Maurer, Gerald; Huber, Kurt; Zeitlinger, Markus; Jilma, Bernd; Wojta, Johann; Speidl, Walter S.

doi:10.1038/srep30162

Cited by 76 publications

(79 citation statements)

References 45 publications

(65 reference statements)

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“…The changes in monocyte subset counts are in agreement with those published previously on the whole monocyte population [13] and on the 3 subsets [14] . However, the larger number of measurements in our study allowed for a better overview of the loss of cells during the first hours after LPS injection and of the increased CM numbers 8 h after LPS injection.…”

Section: Differential Loss Of Monocyte Subsets From Circulation Aftersupporting

confidence: 81%

“…CD11b expression was increased in CM and IM, as published previously [14] , but CD86 and CD62L showed significant changes, pointing towards a lower activation status. A decreased activation state might be due to activated cells homing to the tissues leaving behind less activated cells.…”

Section: Monocyte Activation and Differentiation Markerssupporting

confidence: 65%

“…Using this model, we have previously shown that large numbers of monocytes are transiently lost from the circulation after LPS injection [13] . In addition, the number of all 3 subsets has been shown to be reduced 2 h after LPS injection, whereas the number of IM was increased 24 h after LPS injection [14] . However, a more detailed analysis is required to reveal differences in kinetics of the 3 monocyte subsets and their associated chemokines early in inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

et al. 2017

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Three human monocyte subsets are recognized with different functions in the immune system: CD14⁺⁺/CD16^- classical monocytes (CM), CD14⁺⁺/CD16⁺ intermediate monocytes (IM) and CD14⁺/CD16⁺⁺ non-classical monocytes (NCM). Increased IM and NCM percentages have been reported under inflammatory conditions, yet little is known about monocyte subsets at the onset of inflammation. The human endotoxemia model is uniquely capable of studying the first phases of acute inflammation induced by intravenous injection of 2 ng/kg bodyweight lipopolysaccharide (LPS) into healthy volunteers. After that, monocyte subset counts, activation/differentiation status and chemokine levels were studied over 24 h. The numbers of all subsets were decreased by >95% after LPS injection. CM numbers recovered first (3- 6 h), followed by IM (6-8 h) and NCM numbers (8-24 h). Similarly, increased monocyte counts were observed first in CM (8 h), followed by IM and NCM (24 h). Monocytes did not display a clear activated phenotype (minor increase in CD11b and CD38 expression). Plasma levels of CCL2, CCL4 and CX₃CL1 closely resembled the cell numbers of CM, IM and NCM, respectively. Our study provides critical insights into the earliest stages of acute inflammation and emphasizes the necessity to stain for different monocyte subsets when studying the role of monocytes in disease, as neither function nor kinetics of the subsets overlap.

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Section: Differential Loss Of Monocyte Subsets From Circulation Aftersupporting

confidence: 81%

Section: Monocyte Activation and Differentiation Markerssupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

et al. 2017

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“…A number of inflammatory diseases are selectively associated with the intermediate monocyte subset [11,31–33], and recently, intermediate monocytes were shown to be the major monocyte subset responsive to low level LPS injection in humans [34]. A high level of inflammatory and activation gene expression was identified in the intermediate monocyte subset [15], which may explain why this monocyte subset has been linked to many inflammatory diseases.…”

Section: Discussionmentioning

confidence: 99%

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

Butterfield

Hanna²,

Kaplan³

et al. 2017

Aids

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Objective People living with HIV (PLWH) have chronic immune activation and increased cardiovascular disease (CVD) risk. Activation of monocytes and T lymphocytes causes up-regulation of glucose transporter-1 (GLUT1) for efficient function. PLWH have an increased percentage of GLUT1-expressing monocytes and T lymphocytes, but it is unclear if these cells are associated with CVD. We evaluated expression of GLUT1 and CD38 on monocyte and T lymphocyte populations from HIV-infected women with subclinical CVD. Methods Participants with >75th percentile (n=15) and <25th percentile (n=15) age-adjusted intima-media thickness (IMT) at the right common carotid artery and bifurcation were identified from the Women's Interagency HIV Study. Groups were matched by age, race/ethnicity, smoking status, and CD4 count. All women were receiving suppressive antiretroviral therapy except for one high and one low IMT participant. Monocyte and T lymphocyte populations were evaluated for GLUT1 and CD38 expression using flow cytometry. Results Intermediate monocytes from high IMT women had significantly increased expression of GLUT1 (310 MFI vs. 210 MFI, p=0.024) (66.4% vs. 48.5%, p=0.031) and CD38 (339 MFI vs. 211 MFI, p=0.002) (10.5% vs. 3.8%, p=0.0002) compared to women with low IMT. High and low IMT participants showed no differences in GLUT1 or CD38 expression on classical monocytes, non-classical monocytes, CD4+ and CD8+ T lymphocytes. Conclusion GLUT1-expressing intermediate monocytes are elevated in HIV-infected women with subclinical CVD. These cells may contribute to development of CVD in PLWH and could be a novel target to limit inflammation.

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“…CD11b has been associated with high-fat diet-induced obesity [37], and carotid intima-media thickness [38], and CD11b expression was described as lowest for non-classical monocytes after lipopolysaccharide stimulation [39] and in a rodent model of type 2 diabetes [40]. Results concerning CD36 atherogenicity are also contradictory since an increase [35] or deficiency [41] of its expression have been associated with the pathogenesis of atherosclerosis and CVD.…”

Section: Discussionmentioning

confidence: 99%

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

Leite

Santos

et al. 2017

Obes Facts

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Objective: Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity. Methods: Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO. Results: CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors. Conclusions: WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO.

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Differential in vivo activation of monocyte subsets during low-grade inflammation through experimental endotoxemia in humans

Cited by 76 publications

References 45 publications

Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

Monocyte Subsets Are Differentially Lost from the Circulation during Acute Inflammation Induced by Human Experimental Endotoxemia

Increased glucose transporter-1 expression on intermediate monocytes from HIV-infected women with subclinical cardiovascular disease

Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

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