Studies on the Phagocytic Activity of Human and Rat Polymorphonuclear Cells Exposed to Doxycycline in vivo

Chemotherapy ◽  
1981 ◽  
Vol 27 (6) ◽  
pp. 452-458 ◽  
Author(s):  
Kjetil Melby ◽  
Tore Midtvedt
Author(s):  
R. B. Moyes ◽  
R. E. Droleskey ◽  
M. H. Kogut ◽  
J. R. DeLoach

Salmonella enteritidis (SE) is of great concern to the poultry industry due to the organism's ability to penetrate the intestinal mucosa of the laying hen and subsequently colonize the ovaries and yolk membrane. The resultant subclinical infection can lead to SE infection of raw eggs and egg products. Interference with the ability of the organism to invade has been linked to the activation and recruitment of inflammatory polymorphonuclear cells, heterophils, to the lamina propria of the intestinal tract.Recently it has been established that heterophil activation and increased resistance to SE organ invasion can be accomplished by the administration of SE-immune lymphokines (SE-ILK) obtained from supernatants of concanavalin-A stimulated SE immune T lymphocytes from SE hyperimmunized hens. Invasion of SE into the lamina propria provides a secondary signal for directing activated heterophils to the site of SE invasion.


2011 ◽  
Vol 1 (1) ◽  
pp. 6 ◽  
Author(s):  
Hayet Belmeskine ◽  
Pauline Brousseau ◽  
Sami Haddad ◽  
Louise Vandelac ◽  
Michel Fournier

The immunotoxicological effects of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDDs/Fs) mixtures on <em>Eisenia andrei </em>earthworms have never been studied. In this work we investigated these effects both for <em>in vitro </em>and <em>in vivo</em> exposure, using the viability and the phagocytic activity of coelomocytes as immunological biomarkers and the flow cytometry was used for analysis. The <em>in vitro </em>exposure revealed a cytotoxic effect of PCDD/Fs mixture (C2) containing 50&yen;10-3 ng/mL of 2, 3, 7, 8-TCDD and an induction of the phagocytic capacity at the mixture (C1) containing 25&yen;10-3 ng/mL of 2, 3, 7, 8-TCDD. In the <em>in vivo </em>filter paper exposure, the immunocompetence of earthworms was assessed after 3 h-exposure to mixtures of PCDD/Fs at the levels of C1, C2, C3 and C4 containing about; 0.05, 0.3, 0.5 and 0.83 ng of 2, 3, 7, 8-TCDD/cm&sup2;, respectively. Morphological observations showed an excessive secretion of mucus and body surface lesions in worms exposed to higher concentrations (C3 and C4), which revealed that these organisms were affected by PCDD/Fs either through skin and/or by feeding. The levels of the extruded cell yield decreased significantly at all the concentrations tested. However, the cell viability was shown to be unaffected by PCDD/Fs concentrations. It was also shown, that exposure to the highest PCDD/Fs concentrations; C2, C3 and C4 inhibited both phagocytic activity and efficiency.


2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Dalia Martinez-Marin ◽  
Courtney Jarvis ◽  
Thomas Nelius ◽  
Stéphanie Filleur

Abstract Macrophages have been recognized as the main inflammatory component of the tumor microenvironment. Although often considered as beneficial for tumor growth and disease progression, tumor-associated macrophages have also been shown to be detrimental to the tumor depending on the tumor microenvironment. Therefore, understanding the molecular interactions between macrophages and tumor cells in relation to macrophages functional activities such as phagocytosis is critical for a better comprehension of their tumor-modulating action. Still, the characterization of these molecular mechanisms in vivo remains complicated due to the extraordinary complexity of the tumor microenvironment and the broad range of tumor-associated macrophage functions. Thus, there is an increasing demand for in vitro methodologies to study the role of cell–cell interactions in the tumor microenvironment. In the present study, we have developed live co-cultures of macrophages and human prostate tumor cells to assess the phagocytic activity of macrophages using a combination of Confocal and Nomarski Microscopy. Using this model, we have emphasized that this is a sensitive, measurable, and highly reproducible functional assay. We have also highlighted that this assay can be applied to multiple cancer cell types and used as a selection tool for a variety of different types of phagocytosis agonists. Finally, combining with other studies such as gain/loss of function or signaling studies remains possible. A better understanding of the interactions between tumor cells and macrophages may lead to the identification of new therapeutic targets against cancer.


Parasitology ◽  
1988 ◽  
Vol 96 (1) ◽  
pp. 49-61 ◽  
Author(s):  
D. A. A. Vignali ◽  
Q. D. Bickle ◽  
M. G. Taylor

SUMMARYActively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance toSchistosoma mansonicompared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes (>90%) and platelets (>85%), and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) response to schistosomular antigens (as determined by footpad swelling, 24 h after injection of antigen). However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions (‘foci’) around parasites were essentially similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity (as determined by footpad swelling, 5 h after injection of antigen) nor serum anti-schistosomulum extract antibody levels (as determined by ELISA) were affected. In addition, the pattern of125I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.


2001 ◽  
Vol 281 (5) ◽  
pp. L1210-L1218 ◽  
Author(s):  
Robert Paine ◽  
Susan B. Morris ◽  
Hong Jin ◽  
Steven E. Wilcoxen ◽  
Susan M. Phare ◽  
...  

We hypothesized that pulmonary granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically involved in determining the functional capabilities of alveolar macrophages (AM) for host defense. To test this hypothesis, cells were collected by lung lavage from GM-CSF mutant mice [GM(−/−)] and C57BL/6 wild-type mice. GM(−/−) mice yielded almost 4-fold more AM than wild-type mice. The percentage of cells positive for the β2-integrins CD11a and CD11c was reduced significantly in GM(−/−) AM compared with wild-type cells, whereas expression of CD11b was similar in the two groups. The phagocytic activity of GM(−/−) AM for FITC-labeled microspheres was impaired significantly compared with that of wild-type AM both in vitro and in vivo (after intratracheal inoculation with FITC-labeled beads). Stimulated secretion of tumor necrosis factor-α (TNF-α) and leukotrienes by AM from the GM(−/−) mice was greatly reduced compared with wild-type AM, whereas secretion of monocyte chemoattractant protein-1 was increased. Transgenic expression of GM-CSF exclusively in the lungs of GM(−/−) mice resulted in AM with normal or supranormal expression of CD11a and CD11c, phagocytic activity, and TNF-α secretion. Thus, in the absence of GM-CSF, AM functional capabilities for host defense were significantly impaired but were restored by lung-specific expression of GM-CSF.


Blood ◽  
2010 ◽  
Vol 116 (8) ◽  
pp. 1308-1316 ◽  
Author(s):  
Nupur Bhatnagar ◽  
Henoch S. Hong ◽  
Jayendra K. Krishnaswamy ◽  
Arash Haghikia ◽  
Georg M. Behrens ◽  
...  

Abstract Natural killer (NK) cells and polymorphonuclear cells (PMNs) play a critical role in the first line of defense against microorganisms. Upon host infection, PMNs phagocytose invading pathogens with subsequent killing by oxidative or nonoxidative mechanisms. NK cells are known to have immunoregulatory effects on T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. However, their impact on PMN survival and function is not well known. We found that soluble factors derived from cytokine-activated NK cells delay PMN apoptosis and preserve their ability to perform phagocytosis and produce reactive oxygen species (ROS). The expression patterns of CD11b and CD62L on PMNs differed according to the cytokine combination used for NK-cell stimulation. Irrespective of the NK-cell treatment, however, PMN survival was prolonged with sustained functional capacity. We found that interferon γ, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α produced by NK cells upon stimulation with cytokines played a crucial role in NK cell–mediated effects on PMNs. Our study demonstrates that soluble factors derived from cytokine-activated NK cells send survival signals to PMNs, which would promote their accumulation and function at the site of inflammation in vivo.


2016 ◽  
Vol 5 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Zhaoping Ding ◽  
Sebastian Temme ◽  
Christine Quast ◽  
Daniela Friebe ◽  
Christoph Jacoby ◽  
...  

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3596-3596
Author(s):  
Lilach Lifshitz ◽  
Galit Tabak ◽  
Max Gassman ◽  
Moshe Mittelman ◽  
Drorit Neumann

Abstract Abstract 3596 Poster Board III-533 The immunomodulatory effects of erythropoietin (EPO) on the cellular and humoral compartments of the immune system were originally described by our group in multiple myeloma patients and have been further elucidated in murine experimental models (Mittelman, 2001; Katz 2005; 2007; Prutchi-Sagiv, 2006). However, the mechanisms of action by which EPO affects lymphocyte number and function are still unknown, particularly since lymphocytes do not carry EPO receptors (EPO-R). We thus set to unravel mechanisms underlying the anti-neoplastic immunomodulatory action of EPO. These studies led us to the novel discovery that dendritic cells (DCs) express EPO-R, and that EPO enhances their survival and function (Prutchi-Sagiv, 2008; Lifshitz, 2009). Here we focus on macrophages as an additional EPO target, since in analogy to DCs, macrophages are also antigen presenting cells, and serve as key effectors of the innate immune response. Using murine models, we first explored the in-vivo effects of EPO using recombinant human EPO (rHuEPO, EPREXR, JC)-injected mice, as well as transgenic mice over-expressing human EPO (termed tg6). EPO treatment was associated with an increased splenic macrophage population, detected by F4/80 expression, and an increased number of macrophages expressing CD11b, CD80 and MHC class II. We further explored the effect of in-vivo EPO administration in an inflammatory model exploiting thioglygollate injection to induce recruitment of peritoneal inflammatory macrophages. The inflammatory macrophages obtained from both EPO injected and from tg6 mice displayed increased expression of F4/80, CD11b, CD80 and MHC class II and augmented phagocytic activity, as compared to the control counterparts. These results are supported by in-vitro studies in bone marrow derived macrophages (BMDMs). We show that BMDMs express EPO-R mRNA, as detected by RT-PCR. In-vitro stimulation of the BMDMs with rHuEPO activated multiple signaling pathways including STAT1, STAT5, MAPK, AKT and NFkB indicating macrophage activation via surface EPO-R. EPO treatment of the BMDMs up-regulated their surface expression of CD11b, F4/80 and CD80, as well as enhanced their phagocytic activity. EPO treatment of LPS-stimulated BMDMs augmented IL-12 secretion, and decreased IL-10 secretion. In conclusion our results show that macrophages are direct targets of EPO and that EPO treatment enhances their pro-inflammatory activity and function. These findings point to the multifunctional role of EPO and may advance its clinical applications as an anti-neoplastic immunomodulator. Disclosures: Mittelman: BioGAL- Start up (inactive): Equity Ownership, Patents & Royalties. Off Label Use: Non erythroid effects: immune, anti-cancer (all under investigation).


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