scholarly journals Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Gloria Aranda ◽  
Cristina Lopez ◽  
Rebeca Fernandez-Ruiz ◽  
Yaiza Esteban ◽  
Guillermo Garcia-Eguren ◽  
...  
Keyword(s):  
Immune Cells ◽  
Cardiometabolic Risk ◽  
Cushing Syndrome ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Adrenocorticotrophic Hormone ◽  
Immune Modulator ◽  
Surface Cell Markers ◽  
Hs Crp

Glucocorticoids (GC) induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH) has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC). Aim. To investigate adhesion and activation surface cell markers (CDs) of peripheral IMNC in endogenous Cushing syndrome (CS) and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D), 10 ACTH-independent (ACTH-ID) CS, and 16 healthy controls (C) were included. Leukocytes (Leuc), monocytes (MN), lymphocytes (Lym), and neutrophils (N) were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p<0.05), WC (p<0.001), WHR (p=0.003), BMI (p<0.001), and hs-CRP (p<0.001). CD14++CD16+ (p=0.047); CD14+CD16++ (p=0.053) MN; CD15+ (p=0.027); CD15+CD16+ (p=0.008) N; and NK-Lym (p=0.019) were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5%) versus ACTH-D CS (4.2 ± 1.9%) versus C (4.9 ± 2.3%). NK-Lym correlated with c-LDL (r = 0.433, p=0.039) and CD15+ N with hs-CRP (r = 0.446, p=0.037). In multivariate analysis, Leuc, N, and MN depended on BMI (p=0.021), WC (p=0.002), and WHR (p=0.014), while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p=0.035). Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

scholarly journals The role of cell surface markers and enamel matrix derivatives on human periodontal ligament mesenchymal progenitor responses in vitro

Biomaterials ◽  
2011 ◽  
Vol 32 (30) ◽  
pp. 7375-7388 ◽  
Author(s):  
Philippe Kémoun ◽  
Stan Gronthos ◽  
Malcolm L. Snead ◽  
Jacqueline Rue ◽  
Bruno Courtois ◽  
...  
Keyword(s):  
Cell Surface ◽  
Periodontal Ligament ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Enamel Matrix ◽  
Enamel Matrix Derivatives ◽  
Matrix Derivatives

scholarly journals p53 Is a Crucial Regulator of Hemogenic Endothelial Cell Differentiation from Human Induced Pluripotent Stem Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1085-1085
Author(s):  
Jitendra K. Kanaujiya ◽  
Elizabeth G. Lingenheld ◽  
William C. Skarnes ◽  
Hideyuki Oguro
Keyword(s):  
Stem Cells ◽  
Cell Surface ◽  
Pluripotent Stem Cells ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Hematopoietic Differentiation ◽  
Hematopoietic Stem ◽  
Scientific Advisory ◽  
Induced Pluripotent

Abstract De novo generation of hematopoietic stem cells (HSCs) from human induced pluripotent stem cells (hiPSCs) could provide a virtually unlimited supply of autologous HSCs for clinical transplantation, and offer various approaches that enable gene therapy, drug discovery, disease modeling, and in vitro modeling of human hematopoietic development. However, the derivation of long-term self-renewing HSCs from hiPSCs in culture remains elusive. The tumor suppressor protein p53 plays important roles in normal and malignant hematopoiesis, and Trp53-deficient mice exhibit increased number of HSCs. Although activation of p53 is known to promote differentiation of hPSCs and hPSCs recurrently acquire TP53 dominant negative mutations, its role in hematopoietic differentiation of hiPSCs has not been explored. To differentiate hiPSCs into hematopoietic stem and progenitor cells (HSPCs), we used embryoid body (EB) formation method to first differentiate hiPSCs into hemogenic endothelial (HE) cells that express the CD34 highCD144 +CD73 -CD184 -CD43 -CD235a - cell-surface markers. HE cells were then transferred onto a Matrigel-coated plate to undergo endothelial-to-hematopoietic transition (EHT) to generate HSPCs that express the CD34 midCD45 mid cell-surface markers. Developed HSPCs were functionally evaluated by colony forming assay. We observed that the expression of CDKN1A, a p53 target gene, was upregulated in hiPSC-derived EBs and HSPCs over the course of differentiation. To investigate the role of p53 in the generation of HSPCs from hiPSCs, we genetically deleted TP53 in hiPSCs followed by hematopoietic differentiation. While TP53 deletion increased the growth of EBs, it resulted in severe impairment of differentiation into HE cells and overall production of HSPCs that can form colonies. During HE differentiation from hiPSCs, TP53-deficient EBs showed significant reduction of endothelial-lineage gene expression, such as ETV2, CDH5, and PECAM1, as well as expression of RUNX1, a master transcription factor required for HE specification. These results indicate the indispensable role of p53 in HE differentiation from hiPSCs. We then examined the effect of p53 activation on HE differentiation from hiPSCs by pharmacological activation of p53 in hiPSC-derived cells. Transient activation of p53 by Nutlin-3, a small molecule that inhibits the p53-HDM2 interaction and protects p53 from proteasomal degradation, only during HE differentiation but not during EHT significantly promoted HSPC generation as compared to the vehicle treated control. Our findings shed light on the importance of selecting hiPSC lines that retain normal p53 activity for HE differentiation, and provide an approach to promote hematopoietic differentiation of hiPSCs by transiently activating p53 during HE differentiation. Disclosures Kanaujiya: Synthego: Other: Scientific Advisory; eGenesis: Other: Scientific Advisory.

scholarly journals Differential expression of cell surface markers in response to 2,4-dinitrofluorobenzene in RAW 264.7 and primary immune cells

BMB Reports ◽  
2012 ◽  
Vol 45 (9) ◽  
pp. 538-543 ◽  
Author(s):  
Dong-Bum Kim ◽  
Min-Chul Park ◽  
Byoung-Kwon Park ◽  
Sang-Hoon Kwon ◽  
Joon-Ho Choi ◽  
...  
Keyword(s):  
Cell Surface ◽  
Differential Expression ◽  
Immune Cells ◽  
Raw 264.7 ◽  
Surface Markers ◽  
Cell Surface Markers

scholarly journals Tissue-resident, extravascular CD64-Ly6C- population forms a critical barrier for inflammation in the synovium

2021 ◽  
Author(s):  
Anna B. Montgomery ◽  
Shang Yang Chen ◽  
Gaurav Gadhvi ◽  
Maximilian G. Mayr ◽  
Carla M Cuda ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mononuclear Cell ◽  
Immune Cells ◽  
Cell Biology ◽  
Cell Function ◽  
Myeloid Cell ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Circulating Cells ◽  
Classical Monocytes

AbstractMonocytes are one of the most abundant immune cells infiltrating the inflamed organs. However, the majority of studies on monocytes focus on circulating cells, rather than those in the tissue. Here, we identify and characterize an intravascular (i.v.) and extravascular (e.v.) synovial population (Syn Ly6C- cells) which lack cell surface markers of classical monocytes (Ly6C and CD62) or tissue macrophages (CD64 and Tim4), are transcriptionally distinct and conserved in RA patients. e.v. Syn Ly6C- cells are independent of NR4A1 and CCR2, long-lived and embryonically derived while the i.v. Syn Ly6C- cells are dependent on NR4A1, short lived and derived from circulating NCM. e.v. Syn Ly6C- cells undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. These findings uncover a new facet of mononuclear cell biology and are imperative to understanding tissue-resident myeloid cell function in RA.

scholarly journals Hofbauer cells of M2a, M2b and M2c polarization may regulate feto-placental angiogenesis

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 447-455 ◽  
Author(s):  
J Loegl ◽  
U Hiden ◽  
E Nussbaumer ◽  
C Schliefsteiner ◽  
S Cvitic ◽  
...  
Keyword(s):  
Cell Surface ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Specific Cell ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Placental Angiogenesis ◽  
Hofbauer Cells

The human placenta comprises a special type of tissue macrophages, the Hofbauer cells (HBC), which exhibit M2 macrophage phenotype. Several subtypes of M2-polarized macrophages (M2a, M2b and M2c) exist in almost all tissues. Macrophage polarization depends on the way of macrophage activation and leads to the expression of specific cell surface markers and the acquisition of specific functions, including tissue remodeling and the promotion of angiogenesis. The placenta is a highly vascularized and rapidly growing organ, suggesting a role of HBC in feto-placental angiogenesis. We here aimed to characterize the specific polarization and phenotype of HBC and investigated the role of HBC in feto-placental angiogenesis. Therefore, HBC were isolated from third trimester placentas and their phenotype was determined by the presence of cell surface markers (FACS analysis) and secretion of cytokines (ELISA). HBC conditioned medium (CM) was analyzed for pro-angiogenic factors, and the effect of HBC CM on angiogenesis, proliferation and chemoattraction of isolated primary feto-placental endothelial cells (fpEC) was determined in vitro. Our results revealed that isolated HBC possess an M2 polarization, with M2a, M2b and M2c characteristics. HBC secreted the pro-angiogenic molecules VEGF and FGF2. Furthermore, HBC CM stimulated the in vitro angiogenesis of fpEC. However, compared with control medium, chemoattraction of fpEC toward HBC CM was reduced. Proliferation of fpEC was not affected by HBC CM. These findings demonstrate a paracrine regulation of feto-placental angiogenesis by HBC in vitro. Based on our collective results, we propose that the changes in HBC number or phenotype may affect feto-placental angiogenesis.

Sensitizing Acute Myeloid Leukemia Cells to Interferon-Induced Differentiation By Inhibiting RIP1/RIP3 Necroptotic Pathway

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3752-3752
Author(s):  
Junping Xin ◽  
Dewen You ◽  
Andrew Volk ◽  
Jun Zhang ◽  
Jing Li ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Death Receptor ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
Death Receptor Signaling ◽  
Genetic Deletion ◽  
Acute Myeloid

Abstract Background: In addition to inducing apoptosis, tumor necrosis factor-α (TNFα) and FAS-induced death receptor signaling also induce necroptosis, a recently defined type of programed necrosis, through activation of the RIP1/RIP3-kinase pathway. The role of death receptor signaling-induced apoptosis in the development of leukemia has been well documented. However, the role of necroptotic signaling in the pathogenesis of leukemia has not been studied. Methods: RIP1/RIP3 signaling was inactivated in murine and human acute myeloid leukemia (AML) cells by genetic deletion of RIP1/RIP3 or pharmacologic inhibition using the specific inhibitor Necrostatin-1. The effects of RIP1/RIP3 signal inactivation on the behavior and interferon-γ (IFNγ)-induced differentiation of AML cells were evaluated by morphologic analysis, cell surface markers, in vitro colony-forming ability and in vivo transplantation/leukemogenic capacity. The responses of mice transplanted with Rip1-/- or Rip3-/-murine AML to IFNγ treatment were compared to the mice transplanted with wild-type AML. Results: We found that most types of AML cells produce TNFα and already show basal level activation of RIP1/RIP3 signaling but they do not undergo necroptosis. Using both pharmacological inhibition and genetic deletion techniques, we determined that inactivation of the RIP1/RIP3 signal resulted in partial differentiation of both human AML cell lines and MLL-AF9-transduced murine AML cells as demonstrated by studies of morphology, cell surface markers and colony-forming ability. Rip1 or Rip3 deletion significantly repressed the leukemogenic capacity of murine AML cells in vivo. In addition, inactivation of RIP1/RIP3 signaling significantly enhanced the complete differentiation of AML cells induced by IFNγ. The combination of RIP1/RIP3 inactivation and IFN treatment significantly further attenuated the clonogenic capacity of both primary AML cells and AML cell lines. Such combination treatment also further compromised the leukemogenic ability of AML cells in vivo. Mechanistically, we found that the RIP1/RIP3 pathway regulates the expression of SOCS1, a key negative regulator of IFNγ signaling. Inactivation of RIP1/RIP3 signaling in AML cells renders them hypersensitive to IFNγ -induced monocytic lineage maturation. Conclusion: Resistance to apoptosis is one of the key mechanisms involved in the development of drug resistance in leukemic cells. RIP1/RIP3-mediated necroptosis induced by TNFα has been proposed to be an alternative therapeutic strategy to treat leukemia. However, our studies suggested that inhibition of RIP1/RIP3-mediated necroptotic signaling might be useful strategy for AML treatment when combined with IFNγ. Disclosures No relevant conflicts of interest to declare.

scholarly journals Metabolism Plays a Key Role during Macrophage Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Marion I. Stunault ◽  
Gaël Bories ◽  
Rodolphe R. Guinamard ◽  
Stoyan Ivanov
Keyword(s):  
Fatty Acid ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Macrophage Activation ◽  
Acid Metabolism ◽  
Tissue Homeostasis ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
External Stimuli

Monocyte and macrophage diversity is evidenced by the modulation of cell surface markers and differential production of soluble mediators. These immune cells play key roles in controlling tissue homeostasis, infections, and excessive inflammation. Macrophages remove dead cells in a process named efferocytosis, contributing to the healthy tissue maintenance. Recently, it became clear that the main macrophage functions are under metabolic control. Modulation of glucose, fatty acid, and amino acid metabolism is associated with various macrophage activations in response to external stimuli. Deciphering these metabolic pathways provided critical information about macrophage functions.

PD-L1 Inhibitors for the Treatment of Prostate Cancer

2020 ◽  
Vol 21 (15) ◽  
pp. 1558-1565
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Liang Cheng ◽  
Alessia Cimadamore ◽  
Marina Scarpelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
T Lymphocytes ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Response To Therapy ◽  
Complex Series

The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.

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