CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

Schlitt, Axel; Heine, Gunnar H.; Blankenberg, Stefan; Espinola‐Klein, Christine; Dopheide, Joern F; Bickel, Christoph; Lackner, Karl J.; Iz, Mete; Meyer, J.; Darius, Harald; Rupprecht, Hans J.

doi:10.1160/th04-02-0095

Cited by 240 publications

(117 citation statements)

References 28 publications

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“…Recent analysis using intracellular staining confirmed that CD14 ϩ CD16 ϩ monocytes are major producers of TNF-␣ and possess a higher sensitivity for LPS-induced TNF-␣ production in vivo compared with CD14 ϩϩ CD16 Ϫ monocytes (6,62,64). Therefore, it seems plausible that CD14 ϩ CD16 ϩ monocytes are responding to mild endotoxemia accompanying strenuous exercise (9,50) or EHS (68).…”

Section: Discussionmentioning

confidence: 99%

“…NF-B DNA binding in the liver (11) and intestinal epithelial/mucosal cells (56) is an important source of inflammatory mediators during endotoxemia (11,57) before spillover into the systemic circulation (28). It is possible, however, given the findings by Belge et al (6) and others (62,64) regarding CD14 ϩ CD16 ϩ capacity for LPS-induced TNF-␣ production in vivo, that circulating inflammatory monocytes may be contributing to the changes in circulating cytokine profiles observed during EHS (68).…”

mentioning

confidence: 99%

“…Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82,90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6,62,64,90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the classic subset of monocytes act as scavengers, removing apoptotic cells and aiding in the resolution of inflammation (46).…”

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confidence: 99%

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Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Selkirk GA, McLellan TM, Wright HE, Rhind SG. Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals. Am J Physiol Regul Integr Comp Physiol 296: R575-R586, 2009. First published January 21, 2009 doi:10.1152/ajpregu.90683.2008.-This study examined intracellular cytokine, heat shock protein (HSP) 72, and cellular apoptosis in classic and inflammatory CD14 ϩ monocyte subsets during exertional heat stress (EHS). Subjects were divided into endurance-trained [TR; n ϭ 12, peak aerobic power (V O2peak) ϭ 70 Ϯ 2 ml⅐ kg lean body mass (LBM) Ϫ1 ⅐ min Ϫ1 ] and sedentary-untrained (UT; n ϭ 11, V O2peak ϭ 50 Ϯ 1 ml⅐ kg LBM Ϫ1 ⅐ min Ϫ1 ) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40°C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5°C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0°C/Exh) were analyzed for cytokines (TNF-␣, IL-1␤, IL-6, IL-1ra, and IL-10) in CD14 ϩϩ CD16 Ϫ /CD14 ϩ CD16 ϩ and HSP72/apoptosis in CD14 Bri / CD14 Dim subsets. In addition, serum levels of extracellular (e)HSP72 were also examined. Baseline and Exh samples were separately stimulated with LPS (1 g/ml) or heat shocked (42°C) and cultured in vitro for 2 h. A greater temperature-dependent increase in CD14 ϩ CD16 ϩ cells was observed in TR compared with UT subjects as well as a greater LPS tolerance following in vitro LPS stimulation. TNF-␣ and IL-1␤ cytokine expression was elevated in CD14 ϩ CD16 ϩ but not in CD14 ϩϩ CD16 Ϫ cells. A greater induction of intracellular HSP72 and eHSP72 was observed in TR compared with UT subjects, which coincided with reduced apoptosis at Exh and following in vitro heat shock. Induced HSP in vitro was not uniform across CD14 ϩ subsets. Findings suggest that circulating CD14 ϩ CD16 ϩ , but not CD14 ϩϩ CD16 Ϫ monocytes, contribute to the proinflammatory cytokine profiles observed during EHS. In addition, the enhanced HSP72 response in endurance-trained individuals may confer improved heat tolerance through both anti-inflammatory and anti-apoptotic mechanisms. immune function; cardiovascular/thermoregulatory strain; flow cytometry; heat shock protein PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82, 90). The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6, 62, 64, 90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the clas...

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Section: Discussionmentioning

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confidence: 99%

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confidence: 99%

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Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Selkirk¹,

McLellan²,

Wright³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…CD16? monocytes were seen in the patient cohort [26]. A recent study analyzing coronary artery calcium (CAC) and inflammatory markers found that higher frequencies of CD16?…”

Section: Pathophysiology Of Coronary Artery Disease In Patients With mentioning

confidence: 97%

Coronary Artery Disease in Patients with HIV Infection

Patel

Budoff

2015

Am J Cardiovasc Drugs

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“…Using flow cytometry, the number of circulating CD14 + CD16 ++ monocytes has been shown to be inversely related to plasma HDL levels, and CD16 + monocytes are proportional to the severity of atherosclerosis 142 , whereas a reduction in the monocyte subpopulation is associated with a reduction in intima-media thickness 143 . Again, these measures do not provide any information about to the underlying pathogenesis of disease.…”

Section: Molecular Techniques-mentioning

confidence: 99%

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

Ruparelia¹,

Chai²,

Fisher³

et al. 2017

Nat Rev Cardiol

194

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Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure 'inflammation' are insufficiently precise and do not provide information about disease site, activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including current limitations and challenges that are the focus of ongoing study.Inflammation and its failure to resolve are firmly established as central to the development and complications of several cardiovascular diseases [1][2][3] . Elevated levels of markers of inflammation, such as C-reactive protein (CRP) and serum amyloid A (SAA), have been shown to be predictive of future cardiovascular events across a range of clinical settings [4][5][6] . The role of the innate immune system in the pathogenesis of cardiovascular diseases has been an area of particular focus, with the appreciation that targeting innate immune function Correspondence to R.P.C.: robin.choudhury@cardiov.ox.ac.uk. Author contributionsAll the authors researched data for the article, discussed its contents, and wrote, reviewed, and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Cardiol. Author manuscript; available in PMC 2017 September 01. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript in experimental models can variously attenuate disease progression and injury, and promote healing [7][8][9][10] .Processes of inflammation contribute to a broad range of cardiovascular diseases; however, in this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of known and emerging inflammatory pathways that are thought to be central to their pathogenesis, and the consequences of their activation. We highlight contemporary techniques to characterize and quantify inflammation, and consider h...

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CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-α levels

Cited by 240 publications

References 28 publications

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

Coronary Artery Disease in Patients with HIV Infection

Erratum: Inflammatory processes in cardiovascular disease: a route to targeted therapies

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