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 Nuclear localization of p65 reverses therapy induced senescence

2021 ◽  
pp. jcs.253203
Author(s):  
Sameer Salunkhe ◽  
Saket V. Mishra ◽  
Jyothi Nair ◽  
Sanket Shah ◽  
Nilesh Gardi ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Drug Withdrawal ◽  
Residual Disease ◽  
Primary Cultures ◽  
Cell Formation ◽  
Gene Signature ◽  
Tumor Formation ◽  
Giant Cell Formation

Senescence is a tumor suppressor phenomenon. We have earlier shown that therapy induced senescence in residual disease glioblastoma (GBM) cells can reverse leading to relapse. Here we demonstrate that ciprofloxacin induced senescence in glioma-derived cell lines and primary cultures defined by β-gal positivity, SASP release, giant-cell formation, higher ROS, p-ATM, γ-H2AX, and senescence gene signature have three stages- initiation, pseudo-senescence and permanent-senescence. Drug withdrawal during initiation and pseudo-senescence reinitiated proliferation in vitro and tumor formation in vivo. Importantly, prolonged ciprofloxacin treatment induced permanent-senescence that failed to reverse following drug withdrawal. RNA-Seq revealed downregulated p65 transcription network and incremental SMAD pathway genes expression from initiation to permanent-senescence. Drug withdrawal at initiation and pseudo-senescence but not permanent-senescence increased p65 nuclear localization, and escape from senescence. In contrast, permanent-senescent cells showed loss of nuclear p65 and increased apoptosis. Pharmacological or genetic p65 knockdown upholds senescence in vitro and inhibit tumor formation in vivo. Together, this study demonstrates that levels of nuclear p65 defines the window of therapy induced senescence reversibility and coupling senotherapeutic drugs with p65 inhibitors induce permanent-senescence in GBM cells.

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 217. PROTEINASE 3 PROMOTES MULTINUCLEATE GIANT CELL FORMATION IN GRANULOMATOSIS WITH POLYANGIITIS AND CAN BE MODELLED IN VITRO AND IN VIVO

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_2) ◽  
Author(s):  
Scott Henderson ◽  
Maryam Khosravi ◽  
Harry Horsley ◽  
Alan Greig ◽  
Paul Frankel ◽  
...  
Keyword(s):  
Giant Cell ◽  
Granulomatosis With Polyangiitis ◽  
Cell Formation ◽  
Proteinase 3 ◽  
Multinucleate Giant Cell ◽  
Giant Cell Formation

scholarly journals The induction of cell-mediated immunity and tolerance with protein antigens coupled to syngeneic lymphoid cells.

1979 ◽  
Vol 149 (3) ◽  
pp. 758-773 ◽  
Author(s):  
S D Miller ◽  
R P Wetzig ◽  
H N Claman
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Lymphoid Cells ◽  
Delayed Hypersensitivity ◽  
Cell Mediated Immunity ◽  
Protein Antigens ◽  
Cyt C

A mouse model of cell-mediated immunity (CMI) and tolerance to protein antigens horse gamma globulin (HoGG) and cytochrome (Cyt C) was investigated. A reliable CMI response as measured in vivo by ear swelling or by an in vitro T-cell proliferation assay could be induced by one of two methods: (a) sensitization by antigen-complete Freund's adjuvant in the base of the tail, or (b) sensitization by s.c. injection of antigen coupled to syngeneic lymphoid cells. The in vivo response exhibited characteristic CMI parameters, delayed kinetics, and transfer by viable T cells. Prior i.v. injection of HoGG-modified lymphoid cells (HoGG-LC) or Cyt C-LC before sensitization resulted in a rapidly induced, dose-dependent, antigen-specific suppression of both in vivo and in vitro manifestations of the CMI response. In addition, tolerance in this system was transferrable by an antigen-specific suppressor T cell (Ts). The Ts were found to diminish the in vivo ear swelling reaction in recipient animals, but had no effect on the in vitro T-cell proliferative response of the recipients. In contrast to the rapid development of tolerance in donor mice (phenotypic tolerance), transferrable Ts were first demonstrable 4--7 d posttolerization. This latter result indicates that at least two mechanisms of tolerance are operative in this system: the rapid induction of clone inhibition of reactive T cells and the slower induction of Ts. These results indicate again that the mode of antigen presentation is crucial in determining the immunologic outcome. In these experiments, cell-bound proteins injected subcutaneously led to delayed hypersensitivity while the same antigens injected intravenously led to tolerance. These results are considered in the light of recent experiments which show that T cells recognize antigens on cells in association with major histocompatibility complex products. We believe the following pathways are involved. In sensitization via subcutaneous injection of HoGG-LC, antigen reaches the lymph node via lymphatic pathways which lead to immunogenic macrophage-associated presentation and the activation of delayed hypersensitivity T cells (TDH). In tolerization via intravenous injection of HoGG-LC, antigen (a) reaches the lymph node via the blood, probably directly meeting the TDH, preventing its subsequent activation by immunogenic HoGG (clone inhibition) and (b) reaches the spleen, also via the blood, activating suppressor T cells.

scholarly journals LYMPHOCYTE-MEDIATED CYTOTOXICITY IN VITRO

1971 ◽  
Vol 134 (5) ◽  
pp. 1238-1252 ◽  
Author(s):  
William J. Klein
Keyword(s):  
Lymphoid Cells ◽  
Skin Tumor ◽  
Immunosuppressive Effect ◽  
Cell Mediated Immunity ◽  
Kidney Graft ◽  
Site Of Action ◽  
Antigen Antibody ◽  
Time Of Harvest

The ability of antisera to suppress immune responses either in vivo or in vitro is well known. A variety of lymphocyte-target cell systems have been employed to demonstrate inhibition of cell-mediated immunity by antisera in vitro, and skin, tumor, and kidney graft survival have been prolonged by passively administered antiserum in vivo. An in vitro lymphocyte-tumor cell assay system was developed for the purpose of studying the effects of enhancing antisera (in vivo) on lymphocyte-mediated cytotoxicity in vitro. The characteristics of this system with respect to route of immunization, time of harvest of immune cells, lymphocyte:tumor cell ratio, and effect of nonimmune or nonspecifically immune lymphoid cells are presented. Sera capable of enhancement in vivo were tested in this system and shown to inhibit cell-mediated immunity in vitro. Further, in both instances the immunosuppressive effect is mediated by antigen-antibody complexes and not by free antibody alone. Experiments were also carried out to determine the site of action of these suppressive antigen-antibody complexes. Presensitized lymphocytes were exposed to antigen-antibody complexes, washed, and then allowed to interact with fresh tumor cells (not antibody treated). Lymphocytes treated in this manner are incapable of exhibiting cell-mediated immunity in vitro. This evidence supports the concept that the antigen-antibody complexes have a direct immunosuppressive effect on the lymphocyte.

Bone Marrow Niches for Skeletal Progenitor Cells and their Inhabitants in Health and Disease

2019 ◽  
Vol 14 (4) ◽  
pp. 305-319 ◽  
Author(s):  
Marietta Herrmann ◽  
Franz Jakob
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Adult Stem Cells ◽  
Current Knowledge ◽  
Cell Populations ◽  
Surface Markers ◽  
Bone Marrow Niches

The bone marrow hosts skeletal progenitor cells which have most widely been referred to as Mesenchymal Stem or Stromal Cells (MSCs), a heterogeneous population of adult stem cells possessing the potential for self-renewal and multilineage differentiation. A consensus agreement on minimal criteria has been suggested to define MSCs in vitro, including adhesion to plastic, expression of typical surface markers and the ability to differentiate towards the adipogenic, osteogenic and chondrogenic lineages but they are critically discussed since the differentiation capability of cells could not always be confirmed by stringent assays in vivo. However, these in vitro characteristics have led to the notion that progenitor cell populations, similar to MSCs in bone marrow, reside in various tissues. MSCs are in the focus of numerous (pre)clinical studies on tissue regeneration and repair.Recent advances in terms of genetic animal models enabled a couple of studies targeting skeletal progenitor cells in vivo. Accordingly, different skeletal progenitor cell populations could be identified by the expression of surface markers including nestin and leptin receptor. While there are still issues with the identity of, and the overlap between different cell populations, these studies suggested that specific microenvironments, referred to as niches, host and maintain skeletal progenitor cells in the bone marrow. Dynamic mutual interactions through biological and physical cues between niche constituting cells and niche inhabitants control dormancy, symmetric and asymmetric cell division and lineage commitment. Niche constituting cells, inhabitant cells and their extracellular matrix are subject to influences of aging and disease e.g. via cellular modulators. Protective niches can be hijacked and abused by metastasizing tumor cells, and may even be adapted via mutual education. Here, we summarize the current knowledge on bone marrow skeletal progenitor cell niches in physiology and pathophysiology. We discuss the plasticity and dynamics of bone marrow niches as well as future perspectives of targeting niches for therapeutic strategies.

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