Cytokine Production Precedes the Expansion of Cd14+cd16+ Monocytes in Human Sepsis

Blumenstein, M; Boekstegers, Peter; Fraunberger, Peter; Andreesen, Reinhard; Ziegler‐Heitbrock, H. W. L.; Fingerle‐Rowson, Günter

doi:10.1097/00024382-199707000-00012

Cited by 66 publications

(53 citation statements)

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“…At rest, a majority of the CD14 ϩ CD16 ϩ monocytes are not present in the peripheral circulation but reside in the marginal pool and are released into the peripheral circulation via catecholaminemediated sympathetic mechanisms (78). The time course of peripheral blood inflammatory monocyte expansion during disease (Ͼ50%) (25) has been found to follow systemic cytokine appearance (7,91); however, with physical stress, an immediate mobilization of CD14 ϩ CD16 ϩ cells from the marginal pool is observed (31,78). EHS elicited a similar increase in CD14 ϩ CD16 ϩ subsets, with a greater increase observed in TR subjects.…”

Section: Discussionmentioning

confidence: 99%

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

confidence: 99%

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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“…In contrast, CCR5 was less affected by cytokines [23,38,39]; however, it was up-regulated during maturation of monocytes in adherent culture [26]. The CD14 ϩ CD16 ϩ monocyte subset is expanded in sepsis, where this is preceded by peaks in the production of the monocyte-activating factors TNF-␣, IL-6, and M-CSF [6][7][8]. Moreover, CD14 ϩ CD16 ϩ cells express high levels of pro-inflammatory TNF-␣ but not anti-inflammatory IL-10 in response to LPS [9].…”

Section: Discussionmentioning

confidence: 99%

“…Detailed analysis of CD14 ϩ CD16 ϩ monocytes showed higher MHC class II but lower expression of the ␤ 2 -integrin Mac-1 and CD33, similar to alveolar or monocyte-derived macrophages generated in vitro, confirming that they have acquired features of differentiated monocytes or tissue macrophages [6]. The CD14 ϩ CD16 ϩ monocyte subset is expanded in patients with HIV-1 infection, AIDS dementia, and sepsis, where this is preceded by production of monocyte-activating cytokines, such as tumor necrosis factor ␣ (TNF-␣), monocyte colonystimulating factor (M-CSF), or interleukin-6 (IL-6) [6][7][8]. On the other hand, CD14 ϩ CD16 ϩ CD33 low monocyte subsets express high levels of the proinflammatory cytokine TNF-␣ but no detectable levels of anti-inflammatory IL-10 in response to LPS [9].…”

Section: Introductionmentioning

confidence: 99%

Differential chemokine receptor expression and function in human monocyte subpopulations

Weber

Belge

Hundelshausen

et al. 2000

Journal of Leukocyte Biology

346

257

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The subset of human blood monocytes expressing low levels of CD14 and high levels of CD16 (CD14 ؉ CD16 ؉ ) exhibits features resembling mature tissue macrophages and can be expanded in inflammatory conditions. We analyzed expression of CC chemokine receptors (CCR) in CD14 ؉ CD16 ؉ versus CD14 ؉؉ monocytes, which may be crucial for specific trafficking. Multicolor flow cytometric analysis of whole peripheral blood revealed that, as opposed to CD14 ؉؉ monocytes, the CD14 ؉ CD16 ؉ subset lacked surface expression of monocyte chemotactic protein-1 (MCP-1) receptor CCR2, however, it showed significantly higher surface expression of the macrophage inflammatory protein 1␣ (MIP-1␣)/RANTES receptor CCR5. This was paralleled by differences in mRNA expression in the subsets, as shown by reverse transcriptase-polymerase chain reaction using sorted cells. In comparison to CD14 ؉؉ monocytes, CD14 ؉ CD16 ؉ cells expressed lower CCR2 but higher CCR5 transcript levels, whereas CCR1 levels were equivalent. Flow cytometric analysis of isolated human monocytes recovered after transendothelial chemotaxis assays revealed that the percentage of CD14 ؉ CD16 ؉ cells was dramatically reduced in the fraction migrating toward MCP-1 compared with the fraction that did not migrate or the input, showing that polarized CCR2 expression was accompanied by a differential chemotactic responsiveness. Moreover, CD11b surface expression was preferentially up-regulated by MCP-1 in CD14 ؉؉ cells but by MIP-1␣ in CD14 ؉ CD16 ؉ monocytes, confirming the functional relevance of distinct CCR expression. The characteristics of CD14 ؉ CD16 ؉ cells may reflect preactivation by cytokines and determine their predilective localization during specific inflammatory conditions or susceptibility to infection. J. Leukoc. Biol. 67: 699-704; 2000.

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“…In healthy individuals the CD16 ϩ monocyte subset represents ϳ10% of circulating monocytes, but the proportion of this subset is reportedly increased in a number of pathological conditions including septicemia (38,39), atherosclerosis (40), and reactive arthritis (30). The proportion of CD16 ϩ monocytes is also reportedly elevated in HIV-1-infected individuals with advanced disease (29,41,42) or HIV-associated dementia (41).…”

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confidence: 99%

The CD16+ Monocyte Subset Is More Permissive to Infection and Preferentially Harbors HIV-1 In Vivo

Ellery

Tippett

Chiu

et al. 2007

The Journal of Immunology

305

276

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HIV-1 persists in peripheral blood monocytes in individuals receiving highly active antiretroviral therapy (HAART) with viral suppression, despite these cells being poorly susceptible to infection in vitro. Because very few monocytes harbor HIV-1 in vivo, we considered whether a subset of monocytes might be more permissive to infection. We show that a minor CD16+ monocyte subset preferentially harbors HIV-1 in infected individuals on HAART when compared with the majority of monocytes (CD14highCD16−). We confirmed this by in vitro experiments showing that CD16+ monocytes were more susceptible to CCR5-using strains of HIV-1, a finding that is associated with higher CCR5 expression on these cells. CD16+ monocytes were also more permissive to infection with a vesicular stomatitis virus G protein-pseudotyped reporter strain of HIV-1 than the majority of monocytes, suggesting that they are better able to support HIV-1 replication after entry. Consistent with this observation, high molecular mass complexes of apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G (APOBEC3G) were observed in CD16+ monocytes that were similar to those observed in highly permissive T cells. In contrast, CD14highCD16− monocytes contained low molecular mass active APOBEC3G, suggesting this is a mechanism of resistance to HIV-1 infection in these cells. Collectively, these data show that CD16+ monocytes are preferentially susceptible to HIV-1 entry, more permissive for replication, and constitute a continuing source of viral persistence during HAART.

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Cytokine Production Precedes the Expansion of Cd14+cd16+ Monocytes in Human Sepsis

Cited by 66 publications

References 0 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

Differential chemokine receptor expression and function in human monocyte subpopulations

The CD16+ Monocyte Subset Is More Permissive to Infection and Preferentially Harbors HIV-1 In Vivo

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