scholarly journals Extracellular Lactate Acts as a Metabolic Checkpoint and Shapes Monocyte Function Time Dependently

2021 ◽  
Vol 12 ◽  
Author(s):  
Judith Schenz ◽  
Lena Heilig ◽  
Tim Lohse ◽  
Lucas Tichy ◽  
Katharina Bomans ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Cell Function ◽  
Immune Cell ◽  
Cellular Respiration ◽  
Glycolytic Flux ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Monocyte Function ◽  
Extracellular Lactate ◽  
Intracellular Energy

Elevated blood lactate levels are frequently found in critically ill patients and thought to result from tissue hypoperfusion and cellular oxygen shortage. Considering the close relationship between immune cell function and intracellular metabolism, lactate is more than a glycolytic waste molecule but able to regulate the immune response. Our aim was to elucidate the temporal and mechanistic effect of extracellular lactate on monocytes. To this end, primary human monocytes and the human monocytic cell line MonoMac6 were stimulated with various toll-like-receptor agonists after priming with Na-L-lactate under constant pH conditions. As readout, cytokine production was measured, real-time assessment of intracellular energy pathways was performed, and intracellular metabolite concentrations were determined. Irrespective of the immunogenic stimulus, short-term Na-lactate-priming strongly reduced cytokine production capacity. Lactate and hexoses accumulated intracellularly and, together with a decreased glycolytic flux, indicate a lactate-triggered impairment of glycolysis. To counteract intracellular hyperglycemia, glucose is shunted into the branching polyol pathway, leading to sorbitol accumulation. In contrast, long-term priming with Na-L-lactate induced cellular adaption and abolished the suppressive effect. This lactate tolerance is characterized by a decreased cellular respiration due to a reduced complex-I activity. Our results indicate that exogenous lactate shapes monocyte function by altering the intracellular energy metabolism and acts as a metabolic checkpoint of monocyte activation.

Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line

1997 ◽  
Vol 273 (2) ◽  
pp. L382-L388 ◽  
Author(s):  
M. Koptides ◽  
T. M. Umstead ◽  
J. Floros ◽  
D. S. Phelps
Keyword(s):  
Cell Line ◽  
Cell Function ◽  
Immune Cell ◽  
Surfactant Protein ◽  
Surface Proteins ◽  
Mrna Levels ◽  
Nf Kappa B ◽  
Simultaneous Treatment ◽  
Monocytic Cell ◽  
Monocytic Cell Line

The expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kappa B. We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent increases in tumor necrosis factor-alpha mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung.

Phorbol ester-induced U-937 differentiation: effects on integrin α 5 gene transcription

2000 ◽  
Vol 278 (4) ◽  
pp. L703-L712 ◽  
Author(s):  
Bonnie K. Boles ◽  
Jeffrey Ritzenthaler ◽  
Thomas Birkenmeier ◽  
Jesse Roman
Keyword(s):  
Lung Injury ◽  
Cell Function ◽  
Immune Cell ◽  
Biological Effects ◽  
Surface Expression ◽  
Tumor Promoter ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Monocytic Cell ◽  
Promoter Sequences

Lung injury is accompanied by increased deposition of fibronectin (FN) matrices. Activated monocytic cells recruited to sites of lung injury express integrin receptors for FN that mediate their interaction with this matrix. One such integrin, α5β1, mediates many of the biological effects of FN, and its expression may be important for immune cell function at sites of lung injury. Herein, we examine the expression of α5β1 in response to the tumor promoter phorbol 12-myristate 13-acetate (PMA) in the human promonocytic cell line U-937. We demonstrate that PMA enhanced the adherence of U-937 cells to FN by increasing the expression of both the α5- and β1-subunit mRNAs and the surface expression of the protein. In U-937 cells transfected with an α 5 promoter-reporter gene, we found that PMA induced the transcription of the α 5 gene by acting on very specific promoter sequences other than activator protein-1 in a protein kinase C-dependent manner. Lipopolysaccharide had a similar effect. Modulation of α5β1 expression may be important for regulation of monocytic cell function in lung inflammation after injury.

scholarly journals Haemophilus influenzae Porin Induces Toll-Like Receptor 2-Mediated Cytokine Production in Human Monocytes and Mouse Macrophages

2004 ◽  
Vol 72 (2) ◽  
pp. 1204-1209 ◽  
Author(s):  
Marilena Galdiero ◽  
Massimiliano Galdiero ◽  
Emiliana Finamore ◽  
Fabio Rossano ◽  
Maria Gambuzza ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Adaptor Protein ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Necrosis Factor Alpha ◽  
Human Monocytic Cell Line ◽  
Tnf Α ◽  
Human Monocytic Cell

ABSTRACT The production of proinflammatory cytokines is likely to play a major pathophysiological role in meningitis and other infections caused by Haemophilus influenzae type b (Hib). Previous studies have shown that Hib porin contributes to signaling of the inflammatory cascade. We examined here the role of Toll-like receptors (TLRs) and the TLR-associated adaptor protein MyD88 in Hib porin-induced production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Hib porin-induced TNF-α and IL-6 production was virtually eliminated in macrophages from TLR2- or MyD88-deficient mice. In contrast, macrophages from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, which are defective in TLR4 function, responded normally to Hib porin. Moreover anti-TLR2 antibodies but not anti-TLR4 antibodies significantly reduced Hib porin-stimulated TNF-α and IL-6 release from the human monocytic cell line THP-1. These data indicate that the TLR2/MyD88 pathway plays an essential role in Hib porin-mediated cytokine production. These findings may be useful in the development of alternative therapies aimed at reducing excessive inflammatory responses during Hib infections.

Glucose and Insulin Modulate the Capacity of Endothelial Cells (HUVEC) to Express P-selectin and Bind a Monocytic Cell Line (U937)

2001 ◽  
Vol 86 (08) ◽  
pp. 680-685 ◽  
Author(s):  
Kamal Chettab ◽  
Jacques Duhault ◽  
Elisabeth Koenig-Berard ◽  
John McGregor ◽  
Marta Puente Navazo
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Line ◽  
High Glucose ◽  
Cell Function ◽  
Leukocyte Adhesion ◽  
Human Umbilical Cord ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Endothelial Cell Function

SummaryDiabetes mellitus is associated with increased prevalence of endothelial cell dysfunction and vascular diseases. Mechanisms leading to alterations in endothelial cell function are poorly understood. We report here that hyperglycaemia results in the expression of endothelial adhesion molecules involved in leukocyte adhesion and extravasation. Incubation of human umbilical cord endothelial cells (HUVEC) with 25 mM glucose induced the expression of P-selectin. This effect was reversed by the addition of 1 nM insulin. Moreover, increased ICAM-1 expression was observed upon HUVEC incubation with 25 mM glucose. Increased adhesion of U937 cells (a monocytic cell line) to endothelial cells cultured with 25 mM glucose was observed. High glucose-induced monocytes cell adhesion was inhibited by an anti-P-selectin monoclonal antibody (LYP20). These results show that high glucose concentration activates endothelial cells leading to monocytes adhesion providing further evidence that hyperglycaemia might be implicated in vessel wall lesions contributing to diabetic vascular disease.Present address: Dr. M. D. Puente Navazo, Centre Pluridisciplinaire d’Oncologie, ISREC, Epalinges, Switzerland

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