scholarly journals Association of Malaria-Induced Murine Pregnancy Failure with Robust Peripheral and Placental Cytokine Responses

2009 ◽  
Vol 77 (11) ◽  
pp. 4998-5006 ◽  
Author(s):  
Jayakumar Poovassery ◽  
Julie M. Moore
Keyword(s):  
Tumor Necrosis Factor ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Fetal Loss ◽  
Gamma Interferon ◽  
Pregnancy Failure ◽  
Pregnant Mice ◽  
Necrosis Factor

ABSTRACT Malarial infection in nonimmune pregnant women is a major risk factor for pregnancy failure. The biological mechanisms that underlie malaria-associated fetal loss, however, are poorly understood. Plasmodium chabaudi AS infection during early pregnancy results in midgestational embryonic loss in naive C57BL/6 mice. To define the immunopathogenesis of this malaria-induced pregnancy compromise, cytokine production in plasma, spleen, and placenta cell culture supernatants during the first 11 days of infection and gestation was studied. In infected pregnant mice, systemic interleukin-1β and both systemic and splenic gamma interferon levels were elevated relative to those in uninfected pregnant mice, and gamma interferon was also robustly produced within the placenta 1 to 2 days before malaria-induced fetal loss. Although circulating tumor necrosis factor production was not affected by pregnancy or infection, circulating soluble tumor necrosis factor receptor II was highest in infected pregnant mice, particularly those undergoing abortion, but decreased at the placental level preceding abortion. Systemic levels of interleukin-10 were also high in infected mice at this time point, but this cytokine was not detected at the placental level. Histological examination revealed that trophoblast giant cells of aborting mice phagocytosed infected red blood cells and hemozoin. Furthermore, in vitro-cultured trophoblast cells isolated from embryos on day 7 of gestation phagocytosed P. chabaudi AS-infected red blood cells and secreted tumor necrosis factor. These results suggest that systemic and placenta-level proinflammatory antimalarial immune responses, in the absence of adequate and sustained counterregulatory mechanisms, contribute to pregnancy loss in this model.

Tumor necrosis factor–related apoptosis-inducing ligand 1 (TRAIL1) enhances the transition of red blood cells from the larval to adult type during metamorphosis in Xenopus

Blood ◽  
2010 ◽  
Vol 115 (4) ◽  
pp. 850-859 ◽  
Author(s):  
Kei Tamura ◽  
Shuuji Mawaribuchi ◽  
Shin Yoshimoto ◽  
Tadayoshi Shiba ◽  
Nobuhiko Takamatsu ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Molecular Mechanisms ◽  
Dominant Negative ◽  
Adult Type ◽  
Definitive Erythropoiesis ◽  
Necrosis Factor

Abstract The transition of red blood cells (RBCs) from primitive to definitive erythropoiesis is conserved across vertebrates. In anuran amphibians, the larval RBCs from primitive erythropoiesis are replaced by adult RBCs from definitive erythropoiesis during metamorphosis. The molecular mechanisms by which the primitive (larval) blood cells are specifically removed from circulation are not yet understood. In this study, we identified Xenopus tumor necrosis factor–related apoptosis-inducing ligand 1 (xTRAIL1) and xTRAIL2 as ligands of Xenopus death receptor-Ms (xDR-Ms) and investigated whether TRAIL signaling could be involved in this transition. The Trail and xDR-M genes were highly expressed in the liver and RBCs, respectively, during metamorphosis. Interestingly, xTRAIL1 enhanced the transition of the RBCs, and a dominant-negative form of the xTRAIL1 receptor attenuated it, when injected into tadpoles. Moreover, xTRAIL1 induced apoptosis in larval RBCs, but had little effect on adult RBCs in vitro. We also found that adult RBCs treated with staurosporine, a protein kinase C (PKC) inhibitor, were sensitized to xTRAIL1. The mRNAs for PKC isoforms were up-regulated in RBCs during metamorphosis. These results suggest that xTRAIL1 can cause apoptosis, probably mediated through xDR-Ms, in larval RBCs, but may not kill adult RBCs, presumably owing to PKC activation, as part of the mechanism for RBC switching.

In Vitro Sensitivity of Three Human Renal Tumor Xenografts Towards Tumor Necrosis Factor and Alpha and Gamma Interferon

1989 ◽  
pp. 30-38 ◽  
Author(s):  
A. J. M. C. Beniers ◽  
R. J. A. Van Moorselaar ◽  
W. P. Peelen ◽  
B. T. Hendriks ◽  
U. Otto ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Renal Tumor ◽  
Gamma Interferon ◽  
Tumor Xenografts ◽  
In Vitro Sensitivity ◽  
Necrosis Factor

scholarly journals Gamma-interferon and tumor necrosis factor production after bone marrow transplantation is augmented by exposure to marrow fibroblasts infected with cytomegalovirus

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 1046-1053 ◽  
Author(s):  
AS Duncombe ◽  
A Meager ◽  
HG Prentice ◽  
JE Grundy ◽  
HE Heslop ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Tumor Necrosis Factor ◽  
Marrow Transplantation ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Cmv Infection ◽  
Necrosis Factor

Abstract After bone marrow transplantation (BMT), mortality from viral infections such as cytomegalovirus (CMV) remains high. Gamma-Interferon (gamma IFN) and tumor necrosis factor (TNF) are produced constitutively after BMT and have anti-viral properties. To study the effects of these cytokines on CMV interaction with host cells, we have used patient marrow fibroblasts since marrow stroma is a target for CMV infection correlating with myelosuppression in vivo. Both gamma IFN and TNF are constitutively produced by recipient CD3+ and CD16+ lymphocytes, but not by their marrow fibroblasts. Secretion by peripheral blood mononuclear cells is increased if they are cultured with host fibroblasts infected with CMV in vitro and the levels of gamma IFN and TNF produced are within the range that protects fresh fibroblasts from CMV infection. Constitutive secretion of cytokines by lymphocytes declines by 8 weeks after BMT, a time when the risk of CMV disease increases sharply. The in vitro phenomenon that we have described needs to be evaluated in correlative studies on individual BMT recipients to determine whether such a cytokine-mediated defense mechanism against CMV may operate in vivo.

scholarly journals Defects in hemostasis in P-selectin-deficient mice

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1238-1242 ◽  
Author(s):  
M Subramaniam ◽  
PS Frenette ◽  
S Saffaripour ◽  
RC Johnson ◽  
RO Hynes ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Red Blood Cells ◽  
Tumor Necrosis Factor Alpha ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Bleeding Time ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Deficient Mice ◽  
Necrosis Factor

Recently, our laboratory showed that platelets, like leukocytes, roll on activated endothelium expressing P-selectin, thus suggesting a role for P-selectin in hemostasis (Frenette et at, Proc Natl Acad Sci USA 92:7450, 1995). We report here that the P-selectin--deficient mice show a 40% prolongation of the bleeding time on amputation of the tip of the tail. Moreover, defective hemostasis was observed in a local Shwartzman- like reaction induced by skin injections of lipopolysaccharide followed by tumor necrosis factor-alpha in the P-selectin--deficient mice. The hemorrhagic lesions, quantitated both macroscopically and microscopically, were twofold larger in the P-selectin--deficient mice. This was also confirmed by measuring the radioactivity in the skin using chromium-labeled red blood cells. Therefore, it is evident that P- selectin plays a role in hemostasis as suggested by its support of platelet rolling.

Effect of alpha- and gamma-Interferon and tumor necrosis factor on colony formation of two human renal tumor xenografts in vitro

1988 ◽  
Vol 4 (3) ◽  
pp. 195-198 ◽  
Author(s):  
A. J. M. C. Beniers ◽  
W. P. Peelen ◽  
B. Th. Hendriks ◽  
J. A. Schalken ◽  
F. M. J. Debruyne
Keyword(s):  
Tumor Necrosis Factor ◽  
Colony Formation ◽  
Tumor Necrosis ◽  
Renal Tumor ◽  
Gamma Interferon ◽  
Tumor Xenografts ◽  
Necrosis Factor

Special Collection and Storage Tubes for Blood Endotoxin and Cytokine Measurements

1992 ◽  
Vol 38 (5) ◽  
pp. 764-765 ◽  
Author(s):  
H Redl ◽  
S Bahrami ◽  
G Leichtfried ◽  
G Schlag
Keyword(s):  
Tumor Necrosis Factor ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Blood Collection ◽  
Potential Source ◽  
Special Collection ◽  
And Storage ◽  
Blood Collection Tubes ◽  
Necrosis Factor

Abstract Commercially available blood-collection tubes may be contaminated with endotoxin (315 +/- 95 pg/tube) and could therefore be unsuitable for blood collection for endotoxin measurement. Plasma separation and storage are a potential source of contamination. To avoid contamination and error, we have developed new blood collection tubes that contain heparin free of endotoxin (LPS) and a gel to separate plasma and blood cells. The LPS content is less than 4 pg/tube. Samples can be stored and frozen without plasma withdrawal to preclude contamination. LPS recovery experiments have shown that the new blood-collection tubes do not bind LPS to the separation gel or vial wall. With these tubes, in vitro formation of tumor necrosis factor (404 +/- 163 ng/L in standard tubes vs less than 40 ng/L in special collection tubes) is minimized.

Antineoplastic effects of tumor necrosis factor alone and in combination with gamma-interferon on tumor biopsies in clonogenic assay.

1987 ◽  
Vol 5 (11) ◽  
pp. 1816-1821 ◽  
Author(s):  
S E Salmon ◽  
L Young ◽  
P Scuderi ◽  
B Clark
Keyword(s):  
Lung Cancer ◽  
Bone Marrow ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Malignant Neoplasms ◽  
Tumor Type ◽  
Cancer Resistance ◽  
Necrosis Factor

Tumor colony-forming cells were grown from fresh biopsy specimens from 102 patients with a variety of nonhematologic malignant neoplasms and exposed in vitro to pharmacologically achievable doses of recombinant human tumor necrosis factor (rTNF). In 68 instances, the tumor specimens were also tested against recombinant human gamma-interferon (rIFN-gamma), as well as the combination of rTNF and rIFN-gamma. rTNF exhibited dose-dependent and tumor-type-dependent antitumor effects. Sensitivity to rTNF at doses of less than 100 U was observed in 28% of the tumors tested. A higher than average frequency of sensitivity was observed in colorectal and lung cancer. Resistance to rTNF was observed in 42% of the tumors, including 52% of the ovarian cancer specimens tested. In paired experiments, exposure of tumor specimens to rTNF and rIFN-gamma in combination often resulted in a greater antitumor effect than was observed with either agent alone, with at least subadditive effects seen in 62% of the specimens tested against the combination. Antagonism between rTNF and rIFN-gamma was observed in 18% of the studies. Overall, exposure to the combination of rTNF and rIFN-gamma reduced the dose of rTNF required for significant antitumor activity by about threefold. Normal bone marrow granulocyte-macrophage colony-forming cells were also tested against both rTNF and rIFN-gamma and the combination. The bone marrow progenitors were more sensitive to rTNF and the combination with rIFN-gamma than were the tumor cells; however, the significance of this comparison between two different in vitro assay systems is indeterminate. Based on our observations, rTNF warrants phase II clinical trials in selected solid tumors with definite emphasis on colorectal and lung cancer. Additionally, studies of the combination of rTNF and rIFN-gamma are indicated and will be of particular interest in endometrial and breast cancer.

scholarly journals Massive Destruction of Malaria-Parasitized Red Blood Cells despite Spleen Closure

2005 ◽  
Vol 73 (10) ◽  
pp. 6390-6398 ◽  
Author(s):  
Jürgen Krücken ◽  
Liv I. Mehnert ◽  
Mohamed A. Dkhil ◽  
Manal El-Khadragy ◽  
W. Peter M. Benten ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Tumor Necrosis ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
White Pulp ◽  
Tnf Α ◽  
Necrosis Factor ◽  
Red Pulp

ABSTRACT It is currently accepted that malaria-parasitized red blood cells (pRBC) are eliminated, like senescent erythrocytes, phagocytically by macrophages in the red pulp of the spleen. Here, however, we show that self-healing Plasmodium chabaudi malaria activates spleen closure in C57BL/6 mice. Confocal laser scanning microscopy revealed that spleen closing was manifested by elimination of entry into the red pulp of 3-μm polystyrol particles, pRBC, and nonparasitized red blood cells but not of bovine serum albumin. This spleen closure did not reflect a reduction in the number of phagocytic cells, as shown by flow cytometry, whereas marginal zone macrophages (MZM) were lost and red pulp macrophages entered the white pulp. Splenic trapping of pBRC was strongly reduced in the absence of MZM and marginal metallophilic macrophages (MMM), as it is in noninfected mice with a disrupted lymphotoxin β receptor (LTβR−/−), and it was still significantly reduced when the number of MZM and MMM was diminished, as in tumor necrosis factor alpha-deficient (TNF-α−/−) mice. Moreover, mice deficient in TNF-α, tumor necrosis factor receptor I (TNFRI−/−), and LTβR exhibited progressive impairment in malaria-induced spleen closing. Treatment of C57BL/6 mice with TNF-α induced loss of MZM and spleen closing by about 20%. Our data indicate that TNF/TNFRI signaling is involved in regulating malaria-induced spleen closure, which is maximal during crisis, when parasitemia declines more than 100-fold. Consequently, the vast majority of pRBC cannot be destroyed by the spleen during crisis, suggesting that the known sophisticated sequestration system of Plasmodium parasites did not evolve to avoid splenic clearance.

scholarly journals Gamma-interferon and tumor necrosis factor production after bone marrow transplantation is augmented by exposure to marrow fibroblasts infected with cytomegalovirus

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 1046-1053
Author(s):  
AS Duncombe ◽  
A Meager ◽  
HG Prentice ◽  
JE Grundy ◽  
HE Heslop ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Tumor Necrosis Factor ◽  
Marrow Transplantation ◽  
Tumor Necrosis ◽  
Gamma Interferon ◽  
Cmv Infection ◽  
Necrosis Factor

After bone marrow transplantation (BMT), mortality from viral infections such as cytomegalovirus (CMV) remains high. Gamma-Interferon (gamma IFN) and tumor necrosis factor (TNF) are produced constitutively after BMT and have anti-viral properties. To study the effects of these cytokines on CMV interaction with host cells, we have used patient marrow fibroblasts since marrow stroma is a target for CMV infection correlating with myelosuppression in vivo. Both gamma IFN and TNF are constitutively produced by recipient CD3+ and CD16+ lymphocytes, but not by their marrow fibroblasts. Secretion by peripheral blood mononuclear cells is increased if they are cultured with host fibroblasts infected with CMV in vitro and the levels of gamma IFN and TNF produced are within the range that protects fresh fibroblasts from CMV infection. Constitutive secretion of cytokines by lymphocytes declines by 8 weeks after BMT, a time when the risk of CMV disease increases sharply. The in vitro phenomenon that we have described needs to be evaluated in correlative studies on individual BMT recipients to determine whether such a cytokine-mediated defense mechanism against CMV may operate in vivo.

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