scholarly journals Deriving a Boolean dynamics to reveal macrophage activation with in vitro temporal cytokine expression profiles

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Ricardo Ramirez ◽  
Allen Michael Herrera ◽  
Joshua Ramirez ◽  
Chunjiang Qian ◽  
David W. Melton ◽  
...  
Keyword(s):  
Boolean Network ◽  
Macrophage Activation ◽  
Expression Profiles ◽  
Network Models ◽  
Cytokine Expression ◽  
Boolean Networks ◽  
Experimental Results ◽  
Activated Macrophages ◽  
Activation Patterns

Abstract Background Macrophages show versatile functions in innate immunity, infectious diseases, and progression of cancers and cardiovascular diseases. These versatile functions of macrophages are conducted by different macrophage phenotypes classified as classically activated macrophages and alternatively activated macrophages due to different stimuli in the complex in vivo cytokine environment. Dissecting the regulation of macrophage activations will have a significant impact on disease progression and therapeutic strategy. Mathematical modeling of macrophage activation can improve the understanding of this biological process through quantitative analysis and provide guidance to facilitate future experimental design. However, few results have been reported for a complete model of macrophage activation patterns. Results We globally searched and reviewed literature for macrophage activation from PubMed databases and screened the published experimental results. Temporal in vitro macrophage cytokine expression profiles from published results were selected to establish Boolean network models for macrophage activation patterns in response to three different stimuli. A combination of modeling methods including clustering, binarization, linear programming (LP), Boolean function determination, and semi-tensor product was applied to establish Boolean networks to quantify three macrophage activation patterns. The structure of the networks was confirmed based on protein-protein-interaction databases, pathway databases, and published experimental results. Computational predictions of the network evolution were compared against real experimental results to validate the effectiveness of the Boolean network models. Conclusion Three macrophage activation core evolution maps were established based on the Boolean networks using Matlab. Cytokine signatures of macrophage activation patterns were identified, providing a possible determination of macrophage activations using extracellular cytokine measurements.

scholarly journals Defining tissue- and disease-associated macrophages using a transcriptome-based classification model

2019 ◽  
Author(s):  
Hung-Jen Chen ◽  
Andrew Y.F. Li Yim ◽  
Guillermo R. Griffith ◽  
Wouter J. de Jonge ◽  
Marcel M.A.M. Mannens ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Classification Model ◽  
Chronic Obstructive ◽  
Activated Macrophages ◽  
Obstructive Pulmonary Disease ◽  
Disease Specific

AbstractMacrophages are heterogeneous multifunctional leukocytes which are regulated in a tissue-and disease-specific context. Many different studies have been published using in vitro macrophage models to study disease. Here, we aggregated public expression data to define consensus expression profiles for eight commonly-used in vitro macrophage models. Altogether, we observed well-known but also novel markers for different macrophage subtypes. Using these data we subsequently built the classifier macIDR, capable of distinguishing macrophage subsets with high accuracy (>0.95). This classifier was subsequently applied to transcriptional profiles of tissue-isolated and disease-associated macrophages to specifically define macrophage characteristics in vivo. Classification of these in vivo macrophages showed that alveolar macrophages displayed high resemblance to interleukin-10 activated macrophages, whereas macrophages from patients with chronic obstructive pulmonary disease patients displayed a drop in interferon-γ signature. Adipose tissue-derived macrophages were classified as unstimulated macrophages, but resembled LPS-activated macrophages more in diabetic-obese patients. Finally, rheumatoid arthritic synovial macrophages showed characteristics of both interleukin-10 or interferon-γ signatures. Altogether, our results suggest that macIDR is capable of identifying macrophage-specific changes as a result of tissue-and disease-specific stimuli and thereby can be used to better define and model populations of macrophages that contribute to disease.

scholarly journals High-Affinity Anti-VISTA Antibody Protects against Sepsis by Inhibition of T Lymphocyte Apoptosis and Suppression of the Inflammatory Response

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Tianzhu Tao ◽  
Lulong Bo ◽  
Teng Li ◽  
Longbao Shi ◽  
Hui Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Checkpoint ◽  
Cell Apoptosis ◽  
Expression Profiles ◽  
Cytokine Expression ◽  
Lymphocyte Apoptosis ◽  
T Cell Apoptosis ◽  
High Affinity

Background. B7 family members and ligands have been identified as critical checkpoints in orchestrating the immune response during sepsis. V-domain Ig suppressor of T cell activation (VISTA) is a new inhibitory immune checkpoint involved in restraining T cell response. Previous studies demonstrated that VISTA engagement on T cells and myeloid cells could transmit inhibitory signals, resulting in reduced activation and function. The current study was designed to determine the potential therapeutic effects of a high-affinity anti-VISTA antibody (clone MH5A) in a murine model of sepsis. Methods. Polymicrobial sepsis was induced in male C57BL/6 mice via cecal ligation and puncture. Expression profiles of VISTA on T lymphocytes and macrophage were examined at 24 and 72 h postsurgery. The effects of anti-VISTA mAb on the 7-day survival, lymphocyte apoptosis, cytokine expression, bacterial burden, and vital organ damage were determined. Furthermore, the effects of anti-VISTA mAb on CD3+ T cell apoptosis and macrophage activation were determined in vitro. Results. VISTA was substantially expressed on T cells and macrophages in sham-operated mice; septic peritonitis did not induce significant changes in the expression profiles. Treatment with MH5A improved the survival of septic mice, accompanied by reduced lymphocyte apoptosis, decreased cytokine expression, and enhanced bacterial clearance. Engagement of VISTA receptor with MH5A mitigated CD3+ T cell apoptosis cultured from CLP mice and suppressed LPS-induced cytokine production by macrophage in vitro. Conclusion. The present study identified VISTA as a novel immune checkpoint in the regulation of T cell and macrophage response during sepsis. Modulation of the VISTA pathway might offer a promising opportunity in the immunotherapy for sepsis.

MACROPHAGE ACTIVATION INDUCED BY LYMPHOCYTE MEDIATORS

1975 ◽  
Vol 80 (2_Suppl) ◽  
pp. S245-S261 ◽  
Author(s):  
John R. David
Keyword(s):  
Glucose Oxidation ◽  
Macrophage Activation ◽  
Hexose Monophosphate ◽  
Activated Macrophages ◽  
Migration Inhibition ◽  
Tumoricidal Activity ◽  
Membrane Enzyme ◽  
And Function

ABSTRACT This paper is a brief review of studies which demonstrate that lymphocyte mediators can activate macrophages in vitro. Macrophages which have been incubated in lymphocyte mediator-rich Sephadex fractions show changed morphology, metabolism and function. These changes include an increase in adherence to glass, ruffled membrane movement, phagocytosis of some particles, glucose oxidation through the hexose monophosphate shunt and an increase in the activity of a membrane enzyme, adenylate cyclase. Such mediator-activated macrophages show enhanced bacteriostasis and tumoricidal activity. In addition, studies describing the role of membrane sugars and esterases in the interaction of migration inhibition factor and macrophages are reviewed.

scholarly journals In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection

2021 ◽  
Vol Volume 14 ◽  
pp. 2121-2131
Author(s):  
Ayman Mubarak ◽  
Bahauddeen Alrfaei ◽  
Abdullah Aljurayyan ◽  
Mahfoudh M Alqafil ◽  
Mohamed A Farrag ◽  
...  
Keyword(s):  
Middle East ◽  
Expression Profiles ◽  
Cytokine Expression ◽  
Middle East Respiratory Syndrome ◽  
In Vitro Evaluation

scholarly journals CELL-MEDIATED IMMUNITY AGAINST BESNOITIA AND TOXOPLASMA IN SPECIFICALLY AND CROSS-IMMUNIZED HAMSTERS AND IN CULTURES

1974 ◽  
Vol 139 (3) ◽  
pp. 560-580 ◽  
Author(s):  
Richard L. Hoff ◽  
J. K. Frenkel
Keyword(s):  
Macrophage Activation ◽  
Cell Formation ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Cell Mediated Immunity ◽  
Activated Macrophages ◽  
Specific Effects ◽  
Giant Cell Formation

The capacity of hamster peritoneal cell populations to control viability and growth of Besnoitia and Toxoplasma organisms was assessed in vivo and in vitro. Immunized hamsters reduced the homologous organisms 100- to 10,000-fold over a 5-day period, but the heterologous infection increased 100- to 1,000-fold in numbers, similar as in the nonimmune controls. Passively administered antibody was ineffective although lytic cofactors were supplied by hamsters. In cultures, peritoneal cells from Besnoitia-immune hamsters delayed the growth of homologous parasites to an average of 38.5 h per division; however, in Toxoplasma-immune and nonimmune cells, Besnoitia divided every 12.8 h. Specificity of immunity was pronounced against both infections. With cross-infections, Toxoplasma-immune cultures did not effectively delay Besnoitia growth; however, Besnoitia-immune cultures reduced Toxoplasma growth by one-half. Co-cultivation experiments demonstrated that specifically committed lymphocytes could instruct macrophages to reduce the homologous organism 10-fold, whereas heterologous organisms were reduced only 2-fold. Lymphocyte supernatants initiated hypersensitivity as indicated by macrophage activation and giant cell formation in culture. However, these supernatants did not transfer infection immunity. Lymphokines could account for the hypersensitivity phenomena, but cell-mediated infection immunity in this model required close lymphocyte-macrophage proximity. These studies indicate that a number of distinct processes including delayed hypersensitivity, macrophage activation, and specific cellular immunity are acting simultaneously during latent Besnoitia infection of hamsters. All three processes are mediated by lymphoid cells and appear to be specifically induced. Although activated macrophages develop some heightened nonspecific capabilities, these were several orders of magnitude below the specific effects.

scholarly journals Regulation of arachidonic acid metabolism by macrophage activation.

1982 ◽  
Vol 155 (4) ◽  
pp. 1148-1160 ◽  
Author(s):  
W A Scott ◽  
N A Pawlowski ◽  
H W Murray ◽  
M Andreach ◽  
J Zrike ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Macrophage Activation ◽  
Peritoneal Macrophages ◽  
Arachidonic Acid Metabolism ◽  
Prostaglandin Synthesis ◽  
Activated Macrophages ◽  
Synthetic Enzymes ◽  
Oxygenated Products

Levels of zymosan-induced arachidonic acid (20:4) metabolism by peritoneal macrophages elicited with inflammatory agents and resident macrophages were similar. Thyioglycollate (THIO)-elicited macrophages represented the exception; however, the diminished metabolism by these cells was reproduced by exposing resident cells to 5 mg/ml THIO broth in vitro. In contrast, reduced prostaglandin synthesis by macrophages from mice variously treated with the immunologic agents, Corynebacterium parvum or Bacille Calmette Guérin (BCG), closely correlated with enhanced antitoxoplasma activity, one measure of macrophage activation. This relationship, although not causative, suggested that the capacity for 20:4 metabolism is a function of the macrophage activation state. Modulation of macrophage 20:4 metabolism in vivo apparently required factors in addition to lymphocyte-derived products. Treatment of resident macrophages in vitro with BCG lymphokine was without effect on 20:4 release or prostaglandin synthesis. Activated macrophages from animals inoculated i.p. with C. parvum exhibited reduced 20:4 release and also failed to metabolize 70% of the 20:4 released in response to a zymosan stimulus. Consequently, the quantities of 20:4 metabolites formed were significantly less than expected from 20:4 release. These activated macrophages displayed greatly reduced synthesis of prostacylcin and leukotriene C compared with other 20:4 metabolites. It appeared that factors that regulate macrophage 20:4 metabolism influence the level of the inducible phospholipase and synthetic enzymes for specific 20:4 oxygenated products.

scholarly journals Osthole Attenuates Macrophage Activation in Experimental Asthma by Inhibitingthe NF-ĸB/MIF Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruyi Li ◽  
Peng Song ◽  
Guofang Tang ◽  
Jianghong Wei ◽  
Lizong Rao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Macrophage Activation ◽  
Inflammatory Cells ◽  
Activated Macrophages ◽  
Arginase 1 ◽  
Coumarin Compound ◽  
And Migration ◽  
Cluster Of Differentiation

Inhibition of activated macrophages is an alternative therapeutic strategy for asthma. We investigated whether a coumarin compound, osthole, isolated from Cnidiummonnieri (L.) Cuss, alleviated macrophage activation in vivo and in vitro. Osthole could reduce expression of a marker of activated macrophages, cluster of differentiation (CD)206, in an ovalbumin-challenge model of asthma in mice. Osthole could also inhibit infiltration of inflammatory cells, collagen deposition and production of proinflammatory cytokines [interleukin (IL)-1β, tumor necrosis factor-ɑ, macrophage migration inhibitory factor (MIF)] in asthmatic mice. In vitro, expression of phosphorylated-IĸBɑ, MIF and M2 cytokines (Ym-1, Fizz-1, arginase-1) in IL-4-induced macrophages decreased upon exposure to the NF-ĸB inhibitor MG-132. In our short hairpin (sh)RNA-MIF-knockdown model, reduced expression of M2 cytokines was detected in the IL-4 + shRNA-MIF group. Osthole could attenuate the proliferation and migration of an IL-4-induced rat alveolar macrophages line (NR8383). Osthole could reduce IL-4-induced translocation of nuclear factor-kappa B (NF-ĸB) in NR8383 cells. Collectively, our results suggest that osthole ameliorates macrophage activation in asthma by suppressing the NF-ĸB/MIF signaling pathway, and might be a potential agent for treating asthma.

scholarly journals On the Number of Driver Nodes for Controlling a Boolean Network to Attractors

2018 ◽  
Author(s):  
Wenpin Hou ◽  
Peiying Ruan ◽  
Wai-Ki Ching ◽  
Tatsuya Akutsu
Keyword(s):  
Biological Networks ◽  
Boolean Network ◽  
Network Models ◽  
Boolean Networks ◽  
Reasonable Assumption ◽  
Control Problems ◽  
Expected Number ◽  
Linear Complex ◽  
Simulation Results ◽  
Control Complex

AbstractIt is known that many driver nodes are required to control complex biological networks. Previous studies imply that O(N) driver nodes are required in both linear complex network and Boolean network models with N nodes if an arbitrary state is specified as the target. In this paper, we mathematically prove under a reasonable assumption that the expected number of driver nodes is only O(log2N + log2M) for controlling Boolean networks if the targets are restricted to attractors, where M is the number of attractors. Since it is expected that M is not very large in many practical networks, this is a significant improvement. This result is based on discovery of novel relationships between control problems on Boolean networks and the coupon collector’s problem, a well-known concept in combinatorics. We also provide lower bounds of the number of driver nodes as well as simulation results using artificial and realistic network data, which support our theoretical findings.

scholarly journals Biofilm of Klebsiella Pneumoniae Minimize Phagocytosis and Cytokine Expression by Macrophage Cell Line

2021 ◽  
Author(s):  
Sudarshan Singh Rathore ◽  
Lalitha Cheepurupalli ◽  
Jaya Gangwar ◽  
Thiagarajan Raman ◽  
jayapradha Ramakrishnan
Keyword(s):  
Inflammatory Cytokines ◽  
Cytokine Expression ◽  
Sufficient Information ◽  
Activated Macrophages ◽  
Macrophage Response ◽  
Structural And Functional Properties ◽  
Ifn Γ ◽  
Phagocytic Response

Abstract Infectious bacteria in biofilm mode is involved in many persistent infections. Owing to its importance in clinical settings, many in vitro and in vivo studies are being conducted to study the structural and functional properties of biofilms, their drug resistant mechanism and survival mechanism of planktonic and biofilm cells. In this regard, there is not sufficient information on the interaction between Klebsiella biofilm and macrophages. In this study, we have made an attempt to unravel the interaction between Klebsiella biofilm and macrophages in terms of phagocytic response and cytokine expression. In vitro phagocytosis assays was performed for heat inactivated and live biofilms of K. pneumoniae, together with the expression analysis of TLR2, iNOS, inflammatory cytokines such as IL-β1, IFN-γ, IL-6, IL-12, IL-4, TNF-α and anti-inflammatory cytokines, IL-10. A phagocytic rate of an average of 15% was observed against both heat inactivated and live biofilms, when LPS+IFN-γ activated macrophages were used. This was significantly higher than non-activated macrophages when tested against heat inactivated and live biofilms (average 8%). Heat-inactivated and live biofilms induced similar phagocytic response and up-regulation of pro-inflammatory genes in macrophages, indirectly conveying that macrophage response is to some extent dependent on the biofilm matrix.

scholarly journals MK2 mediates macrophage activation and acute lung injury by regulating let-7e miRNA

2018 ◽  
Vol 315 (3) ◽  
pp. L371-L381 ◽  
Author(s):  
Yaxian Wu ◽  
Huiqiong He ◽  
Yunhe Ding ◽  
Sirui Liu ◽  
Depeng Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Macrophage Activation ◽  
Critical Role ◽  
Protein A ◽  
Cytokine Expression ◽  
Conditional Knockout ◽  
Lps Challenge ◽  
Tnf Α

MAPK-activated protein kinase 2 (MK2) plays a critical role in the development of inflammation. However, the modulatory mechanisms in macrophage activation and acute lung injury (ALI) have not been completely defined. Here, we reported that MK2-deficient mice (MK2−/−) protected against sepsis-induced ALI. In response to lipopolysaccharide (LPS) challenge, MK2−/− mice and myeloid cell-specific MK2 conditional knockout mice (MK2Lyz2-KO) exhibited attenuated inflammatory response, especially producing fewer amounts of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and macrophage inflammatory protein 2 (MIP-2). LPS treatment in vitro resulted in reduced cytokine expression in MK2−/− bone marrow-derived macrophages (BMDMs). Furthermore, we found that LPS-induced microRNA lethal-7e ( let-7e) expression was significantly increased in MK2−/− macrophages. Transfection of let-7e antagomirs into MK2−/− BMDM rescued LPS-induced expression of TNF-α, IL-6, and MIP-2. In contrast, transfection of let-7e mimics into MK2+/+BMDM decreased cytokine expression. Meanwhile, LPS-induced phosphorylation of cAMP response element-binding (CREB) protein, a substrate of MK2, was downregulated in MK2−/− BMDMs. Lin28, an inhibitory molecule of let-7, was significantly reduced in MK2−/− macrophages. Our results suggested that MK2 boosts LPS-induced macrophage activation and ALI via increasing activation of CREB and consequently, the expression of Lin28 and downregulation of let-7e.

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