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Fibroblast and Immune Cell Cross Talk in Cardiac Repair
Published in Shyam S. Bansal, Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Stelios Psarras, Georgina Xanthou
The manipulation of the immune response is of paramount importance for cardiac output and HF fate (1). On the other hand, certain arms of the inflammatory response are definitively beneficial. When CD14+-activated macrophages were intramyocardi-ally co-delivered along with CD90+ MSCs in patients with HF of ischemic etiology, a 37% reduction in adverse cardiac events was achieved (115). Moreover, when murine hearts undergoing ischemia reperfusion were injected with fractionated BM mono-nuclear cells or c-Kit+ cardiac progenitor cells (CPCs), the mechanical properties of the infarcts were ameliorated and the extent of fibrosis was reduced (116). Notably, the same outcome was achieved by injecting zymosan, a cell-free agent activating the innate immune response. Mechanistically, the overall benefits could be attributed to the accumulation of two distinct populations of macrophages (CCR2+ and CXC3R1+) in murine hearts (116). When these populations were isolated and co-cultured with cardiac fibroblasts, CCR2+ macrophages induced the expression of collagen type I, αSMA, and the collagen cross-linking regulator lysyl oxidase (encoded by Lox) in stromal cells, while CXC3R1+ macrophages induced the expression of connective tissue growth factor (CTGF), a profibrotic molecule acting downstream of TGFβ1 (Figure 5.2).
Interleukin-1 Inhibitors and Their Significance in Rheumatoid Arthritis
Published in Thomas F. Kresina, Monoclonal Antibodies, Cytokines, and Arthritis, 2020
Gloria C. Higgins, Arnold E. Postlethwaite
Tiku and coworkers (154) have reported a factor from lysates and culture supernatants of human polymorphonuclear leukocytes (PMN) that suppresses the response of mouse thymocytes to partially purified human IL-1 and PHA. Inhibition could be partially overcome by increasing amounts of IL-1. Synthesis of this inhibitor was increased by zymosan stimulation of PMN and occurred in the absence of serum. Addition to protease inhibitors to PMN lysate did not alter its ability to inhibit IL-1. When ConA was used in place of PHA in the comitogenesis assay, the PMN inhibitor was active in the presence or absence of IL-1. When thymocytes were maximally stimulated by higher concentrations of ConA, however, the inhibitor was inactive. No inhibition of IL-2-induced proliferation of the CTLL-2 cell line was observed. When zymosan-stimulated PMN lysates or supernatants were fractionated on gel filtration, the IL-1 inhibitor appeared in two peaks: one greater than 160 kD, possibly representing aggregates, and one at about 70 kD (supernatant) or 45-70 kD (lysate). This inhibitor has not been further characterized.
Why Does Moderate Exercise Enhance, But Intense Training Depress, Immunity ?
Published in Husband Alan J., Behaviour and Immunity, 2019
John A. Smith, Scott J. McKenzie, Richard D. Telford, Maurice J. Weidemann
Sterile Hank’s balanced salt solution containing 5mM D-glucose (HBSS) and phosphate buffered saline (PBS) were prepared by conventional methods. Luminol was prepared as a chemiluminogenic indicator by suspending 10 mg of luminol (5-amino-2,3-dihydro-l,4-phthalazinedione) (Boehringer, Mannheim, FRG) in 5ml of PBS containing 8mM triethylamine. The mixture was sonicated for 1 minute and shaken to give a clear solution. A single batch of opsonized zymosan (used for all experiments) was prepared by incubating 10 mg of Zymosan-A particles (highly glycosylated fragments of yeast cell walls) (Sigma. St Louis, MO:) with 1 ml of fresh human plasma for 30 min at 37°C. The suspension was centrifuged at 400 χ g for 2 minutes and the pellet washed twice in PBS before resuspension at a final concentration of 10 mg/ml. Aliquots (1ml) were stored frozen and used only once after thawing. Counting by haemocytometer revealed that this preparation contained approx. 106 zymosan particles/microlitre.
Neonatal vaccine effectiveness and the role of adjuvants
Published in Expert Review of Clinical Immunology, 2019
Isaac G. Sakala, Katherine Marie Eichinger, Nikolai Petrovsky
As noted previously, BCG is one of the few vaccines that are effective in newborns. BCG expresses glycolipids, glycopeptides and other sugar-based structures that are potent activators of the innate immune system. The success of BCG raises the question of whether sugar-based immune activators may be able to preferentially activate the neonatal immune system. Trehalose 6,6ʹ-dibehenate (TDB) is a synthetic analog of mycobacterially-expressed trehalose-6,6-dimycolate (TDM) that targets the PAMP receptor, MINCLE (macrophage inducible Ca2+-dependent lectin receptor). TDB was shown to activate human newborn DCs and enhanced Th1 polarizing cytokine production by DCs when given in combination with a TLR7/8-ligand [116]. TDB enhanced protection against influenza in immunized neonatal mice through the induction of Tfh cells and high-affinity plasma cells [110]. CAF01, a cationic adjuvant formulation consisting of TDB in dimethyl dioctadecyl ammonium (DDA) delivery vehicle successfully induced Th1/Th17 responses in murine neonates [117]. Curdlan, a water-insoluble linear beta-1,3-glucan produced by bacteria was also been shown to enhance Th1 responses to a subunit TB vaccine [110] and an influenza vaccine in neonatal mice [118]. Zymosan, a glucose-based polysaccharide expressed by yeast that activates multiple PAMP receptors including TLR2 and the glucan receptor, induced comparable cytokine levels in cord blood and adult blood monocytes and DCs [119], raising the possibility it may also be an effective neonatal adjuvant.
Anti-inflammatory potential of pyocyanin in LPS-stimulated murine macrophages
Published in Immunopharmacology and Immunotoxicology, 2019
José Marreiro de Sales-Neto, É. A. Lima, L. H. A. Cavalcante-Silva, U. Vasconcelos, S. Rodrigues-Mascarenhas
Intraperitoneal injection of zymosan A, a polysaccharide component of cell wall from Saccharomyces cerevisiae, represents a self-resolving model of acute inflammation. Zymosan A, recognized by toll-like receptor-2 (TLR2) and dectin-1 receptor [65], induces vascular permeability increase, one of the primary signs of inflammation, which appears within 30 min after the inflammatory stimulus due to the activation of resident macrophages and mast cells, by histamine, prostaglandin E2, prostaglandin F1α, and leukotriene release [31,66–70]. At the 4th hour of peritonitis, there is a massive polymorphonuclear (PMN) leukocytes influx with maximal cell accumulation [32,68,71]. Here, pyocyanin pretreatment (5 mg/kg i.p.) was not able to affect PMNs influx after 4 h. In other studies, pyocyanin intranasal treatment (1 mg/kg) for 3 weeks generated cystic fibrosis phenotype in C57BL-6 and Stat6–/– mice [40] and concomitant instillation of pyocyanin (0.3 mg/kg) and 1-hydroxyphenazine 24 h before euthanasia initiated inflammatory response in sheep airways, with neutrophils influx and albumin increase in bronchoalveolar lavage [23]. Thus, our findings suggest that pyocyanin exerts anti-inflammatory effects on murine peritoneal macrophages, downregulating nitric oxide, TNF-α, and IL-1β levels, which seems to be independent of cell migration. These effects may represent a mechanism of immune evasion; nevertheless, more detailed studies should be performed to confirm this hypothesis.
A model to study complement involvement in experimental retinal degeneration
Published in Upsala Journal of Medical Sciences, 2018
Camilla Mohlin, Kerstin Sandholm, Anders Kvanta, Kristina N. Ekdahl, Kjell Johansson
Conditioned media from the various samples were investigated for fluid-phase anaphylotoxin C3a and for sC5b-9 by sandwich ELISA. The amount of generated C3a was measured with monoclonal antibody (mAB) anti-C3a 4SD17.3 as the capture antibody and polyclonal biotinylated anti-C3a (70). Detection of sC5b-9 complexes was made using mAB anti-neoC9 aEII (Diatec Monoclonals AS, Oslo, Norway) as the capture antibody (71) and detected with a sheep polyclonal anti-C5 antibody (Acris Antibodies GmbH, Herford, Germany). The abovementioned complexes were detected with HRP-conjugated streptavidin (GE Healthcare, Uppsala, Sweden). Zymosan-activated serum served as a standard for the analysis, and pooled diluted zymosan-activated serum from blood donors was used as a control.