Prostaglandin Regulation of Macrophage Function
Gloria H. Heppner, Amy M. Fulton in Macrophages and Cancer, 2019
Macrophage activation in response to immunological, as well as nonimmunological stimuli is a complex, dynamic process initiated when the cell comes in contact with an external signal via plasma membrane receptors. Transmission of external signals through the plasma membrane into the cytoplasmic compartment is mediated by a number of regulatory pathways. Ligand-receptor interaction can result in depolarization of the plasma membrane,53 fluxes in intracellular calcium levels,54 turnover of plasma membrane phospholipid,55,56 increased levels of cGMP, and activation of membrane-bound adenylate cyclase.58 In the macrophage several studies have shown that intracellular levels of cAMP are modulated in response to stimulation with various hormones. Similarly, treatment of macrophages with a number of agents identified as having a role in activation or associated with the acquisition of various effector functions, also results in modulation of cAMP levels in the cell.
Applications of tissue phenomics
Gerd Binnig, Ralf Huss, Günter Schmidt in Tissue Phenomics, 2018
A recent approach used imaging mass cytometry to survey an entire cancer indication, clear-cell renal cell carcinoma (ccRCC), characterize the types of TME present, and identify potential biomarkers and targets for immunotherapy (Chevrier et al., 2017). The method combines atomic mass spectrometry and flow cytometry in high spatial resolution on histological specimens. A panel of 39 markers included a number of canonical T and B cell markers, like CD8, CD4, and CD20, immunomodulatory molecules like PD-1, TIM-3, CTLA-4, and LAG-3, but also a number of newly designed macrophage markers for differentiating in detail the macrophage subsets in the samples. A key learning was that the structure of the immune landscape directly allowed to stratify patients by applying a correspondence analysis that captures the complexity of relationships between immune cell species within the TME. Other findings showed that while PD-1 is broadly expressed across T-cell species, other important targets such as CTLA-4 are much lower expressed and might, therefore, be less effective in immunotherapy, and CD38, known as marker of T-cell exhaustion in infectious diseases, might also play a crucial role in ccRCC.
Reduction and Fixation of Sacroiliac joint Dislocation by the Combined Use of S1 Pedicle Screws and an Iliac Rod
Kai-Uwe Lewandrowski, Donald L. Wise, Debra J. Trantolo, Michael J. Yaszemski, Augustus A. White in Advances in Spinal Fusion, 2003
Fresenius, Bad Homburg, Germany) in a cylinder and allowed to rest for 30 min at 37°C to permit the sedimentation of erythrocytes. The resulting supernatant was centrifuged at 400 g for 7.5 min, and the pellet was washed and suspended in PBS. This cell suspension was loaded carefully onto three volumes of Ficoll-sodium metrizoate (Lymphoprep; Nyegaerd, Oslo, Norway; density = 1.077 g/mL) and centrifuged at 400 g for 30 min. The layer of mononuclear cells was washed and suspended in Hanks’ balanced salt solution, supplemented with 0.5% human serum albumin (HBSS + 0.5% HAS), and used as a monocyte source. Monocytic cells were allowed to adhere to the surface of the plastic tissue culture vessel during incubation at 37°C for 16 h and were separated from non-adherent lymphocytic cells by being washed with prewarmed PBS/1% (v/v) FCS. Growth medium was added to the adherent cell cultures, which were then incubated at 37°C in a humidified atmosphere with 6% (v/v) C02 until ready for use. Cells were examined at 3 days postplating, at which time they had differentiated into monocyte-derived macrophages, regardless of their incubation temperature. More than 95% of the adherent cells were macrophages, defined by the recently identified KP-1 (CD68) (DAKO) mature macrophage marker [12]. Finally, color development was established by treating macrophages with AEC (DAKO) at room temperature for 5 min. Alamar Blue Assay
A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy
Published in OncoImmunology, 2020
Ana Victoria Casadesús, Claire Deligne, Béré Kadjdiatou Diallo, Katya Sosa, Nathalie Josseaume, Circe Mesa, Kalet León, Tays Hernández, Jean-Luc Teillaud
We next explored the effect of combination treatment with anti-CD20 antibody and IL-2 or no-alpha mutein on macrophages (MΦ, defined as CD11b+CD11c−Gr1lowF4/80+), at day 14. These cells have been shown to be important effectors following anti-CD20 therapy38 and are also involved in the generation of anti-tumor T-cell memory response.27 A significant increase in the number of MΦ was observed in the group treated with anti-CD20 and no-alpha mutein, but not with the IL-2 treatment (Figure 6(a)). Furthermore, in these animals, an increased expression of the major histocompatibility complex class II (MHCII) molecules and of CD16/CD32 (mouse FcγRII, FcγRIII) and FcγRIV on MΦ (Figure 6(b,c)) was detected. The rise in the expression of these molecules are a hallmark of macrophage activation.
Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease
Published in Expert Opinion on Therapeutic Targets, 2021
Yaoyao Du, Lan Rong, Yuanhua Cong, Lan Shen, Ning Zhang, Bing Wang
M1 macrophages are activated by granulocyte-macrophage colony stimulating factor (GM-CSF), Toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS) or Th1-type cytokines such as interferon-γ (IFN-γ) [32]. These cells highly express CD64, CD86, and human leukocyte DR antigen (HLA-DR antigen). The transformation of macrophages into the M1 phenotype involves many key transcription factors (Figure 1), such as Janus kinase/signal transducer and transcription activator 1 (JAK/STAT1) [33,34], phosphoinositide 3-kinase (PI3K)/Akt1 [35,36], nuclear factor (NF)-κB [37,38], interferon regulatory factor 5 (IRF5) [39], and Notch [40,41]. In the early phase of the inflammatory response, M1 macrophages engulf foreign pathogens and clear bacteria and cellular debris from the wound [42]. However, the secretion of more pro-inflammatory cytokines (e.g. TNF-α, interleukin-6/12/23 [IL-6/12/23]) and high levels of inducible nitric oxide synthesis (iNOS) and reactive oxygen species (ROS) ultimately aggravate the inflammatory response and also cause tissue damage and impaired wound healing [42–44].
Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma
Published in OncoImmunology, 2019
Shasha Liu, Chaoqi Zhang, Nomathamsanqa Resegofetse Maimela, Li Yang, Zhen Zhang, Yu Ping, Lan Huang, Yi Zhang
Furthermore, Macrophage Scavenger Receptor1 (MSR1), also known as CD204 has additionally been identified as a specific marker for TAMs.40,41 It was also reported that CD14, CD68, CD11B are macrophage markers.15 To fully understand the relationship between CD163 and other macrophage markers, Pearson correlation analysis was performed. As Figures S6A and B indicated, CD163 showed a high correlation with the macrophage marker members both in the CGGA RNA-seq and microarray databases. In line with the CGGA database, the correlation between CD163 and other macrophage markers was also robustly positive in the TCGA database (Figure S6c). Similar results were observed in Figures S6(d-f). Taken together, these results point to the rising MSR1, CD11B, or CD68 levels in cases when glioma patients acquire resistance to therapy of targeting CD163.
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