Exposure of alveolar macrophages to polybrominated diphenyl ethers suppresses the release of pro-inflammatory products in vitro

2012 ◽  
Vol 237 (4) ◽  
pp. 429-434 ◽  
Author(s):  
Stephen R Hennigar ◽  
Jay L Myers ◽  
Anthony R Tagliaferro
Keyword(s):  
Estrogen Receptor ◽  
Alveolar Macrophages ◽  
Polybrominated Diphenyl Ethers ◽  
Diphenyl Ether ◽  
Prostaglandin E ◽  
Tnf Α ◽  
Diphenyl Ethers ◽  
The Impact

Inhalation of chemical pollutants has been associated with a reduced immune response in humans. Inhalation of dust is a major route of exposure for one endocrine-disrupting chemical and suspected xenoestrogen, polybrominated diphenyl ethers (PBDEs); however, the impact of PBDEs on immune function is unclear. The objective of this study was to investigate the action of PBDEs on cytokine and eicosanoid release by alveolar macrophages and determine whether the effects are mediated via the estrogen receptor. The production of tumor necrosis factor (TNF)- α, interleukin (IL)-6, IL-1 β, IL-10 and prostaglandin E2 (PGE2) by porcine alveolar macrophages exposed to different concentrations of the pentabrominated diphenyl ether mixture, DE-71, were measured; cells were also exposed to varying concentrations of 17 β-estradiol and the selective estrogen receptor-modulating agent, tamoxifen. Cells exposed to PBDEs released significantly less pro-inflammatory cytokines (TNF- α and IL-6) and PGE2 compared with controls; IL-1 β and IL-10 were not detected in the culture medium. Cells exposed to 17 β-estradiol released significantly less TNF- α compared with controls, an effect that was reversed by the addition of tamoxifen; tamoxifen had no effect on the inhibition of TNF- α release by PBDEs. Although the suppression of TNF- α with DE-71 was similar to that of estrogen, the inhibitory effects of DE-71 were not found to be dependent on the estrogen receptor. Findings of this study suggest that chronic exposure to PBDEs suppressed innate immunity in vitro. Whether the immunosuppressant effects of PBDEs occur in vivo, remains to be determined.

Impaired functional activity of alveolar macrophages from GM-CSF-deficient mice

2001 ◽  
Vol 281 (5) ◽  
pp. L1210-L1218 ◽  
Author(s):  
Robert Paine ◽  
Susan B. Morris ◽  
Hong Jin ◽  
Steven E. Wilcoxen ◽  
Susan M. Phare ◽  
...  
Keyword(s):  
Host Defense ◽  
Alveolar Macrophages ◽  
Phagocytic Activity ◽  
Wild Type ◽  
Specific Expression ◽  
Gm Csf ◽  
Functional Capabilities ◽  
Tnf Α

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.

The effects in vitro of TNF-α and its antagonist ‘etanercept’ on ejaculated human sperm

2017 ◽  
Vol 29 (6) ◽  
pp. 1169 ◽  
Author(s):  
Nicola A. Pascarelli ◽  
Antonella Fioravanti ◽  
Elena Moretti ◽  
Giacomo M. Guidelli ◽  
Lucia Mazzi ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
In Vitro Study ◽  
Human Sperm ◽  
Dna Integrity ◽  
Sperm Function ◽  
Sperm Viability ◽  
Tnf Α ◽  
The Impact

Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500 ng mL–1) and etanercept (from 800 µg mL–1 to 2000 µg mL–1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200 µg mL–1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng mL–1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.

scholarly journals Characterization of the Plasmacytoid Dendritic Cell Response to Transmitted/Founder and Nontransmitted Variants of HIV-1

2018 ◽  
Vol 92 (19) ◽  
Author(s):  
Jordan Ari Schwartz ◽  
Hongliang Zhang ◽  
Zachary Ende ◽  
Martin J. Deymier ◽  
Terry Lee ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Female Genital Tract ◽  
Enzyme Linked Immunosorbent Assay ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
The Impact ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection often arises from a single transmitted/founder (TF) viral variant among a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically nondominant in blood and genital secretions, indicating that they have unique traits. The plasmacytoid dendritic cell (pDC) is the primary alpha interferon (IFN-α)-producing cell in response to viral infections and is rapidly recruited to the female genital tract upon exposure to HIV-1. The impact of pDCs on transmission is unknown. We investigated whether evasion of pDC responses is a trait of TF viruses. pDCs from healthy donors were stimulated in vitro with a panel of 20 HIV-1 variants, consisting of one TF variant and three nontransmitted (NT) variants each from five transmission-linked donor pairs, and secretion of IFN-α and tumor necrosis factor alpha (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). No significant differences in cytokine secretion in response to TF and NT viruses were observed, despite a trend toward enhanced IFN-α and TNF-α production in response to TF viruses. NT viruses demonstrated polarization toward production of either IFN-α or TNF-α, indicating possible dysregulation. Also, for NT viruses, IFN-α secretion was associated with increased resistance of the virus to inactivation by IFN-α in vitro, suggesting in vivo evolution. Thus, TF viruses do not appear to preferentially subvert pDC activation compared to that with nontransmitted HIV-1 variants. pDCs may, however, contribute to the in vivo evolution of HIV-1. IMPORTANCE The plasmacytoid dendritic cell (pDC) is the first cell type recruited to the site of HIV-1 exposure; however, its contribution to the viral bottleneck in HIV-1 transmission has not been explored previously. We hypothesized that transmitted/founder viruses are able to avoid the pDC response. In this study, we used previously established donor pair-linked transmitted/founder and nontransmitted (or chronic) variants of HIV-1 to stimulate pDCs. Transmitted/founder HIV-1, instead of suppressing pDC responses, induced IFN-α and TNF-α secretion to levels comparable to those induced by viruses from the transmitting partner. We noted several unique traits of chronic viruses, including polarization between IFN-α and TNF-α production as well as a strong relationship between IFN-α secretion and the resistance of the virus to neutralization. These data rule out the possibility that TF viruses preferentially suppress pDCs in comparison to the pDC response to nontransmitted HIV variants. pDCs may, however, be important drivers of viral evolution in vivo.

scholarly journals Lipoxin (LX)A4 and Aspirin-triggered 15-epi-LXA4 Inhibit Tumor Necrosis Factor 1α–initiated Neutrophil Responses and Trafficking: Regulators of a Cytokine–Chemokine Axis

1999 ◽  
Vol 189 (12) ◽  
pp. 1923-1930 ◽  
Author(s):  
Mohamed Hachicha ◽  
Marc Pouliot ◽  
Nicos A. Petasis ◽  
Charles N. Serhan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Gm Csf ◽  
Tnf Α ◽  
Human Polymorphonuclear Leukocytes ◽  
The Impact ◽  
Receptor Antibodies ◽  
Necrosis Factor

The impact of  lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-α–initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1–10 nM, the LXA4 and ATL analogues each inhibited TNF-α–stimulated superoxide anion generation and IL-1β release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-α, as these responses were not altered with either GM-CSF– or zymosan-stimulated cells. TNF-α–induced IL-1β gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-α–stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1β, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-α–directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

scholarly journals Scavenger Receptor A Dampens Induction of Inflammation in Response to the Fungal Pathogen Pneumocystis carinii

2007 ◽  
Vol 75 (8) ◽  
pp. 3999-4005 ◽  
Author(s):  
Melissa Hollifield ◽  
Elsa Bou Ghanem ◽  
Willem J. S. de Villiers ◽  
Beth A. Garvy
Keyword(s):  
Alveolar Macrophages ◽  
Pneumocystis Carinii ◽  
Scavenger Receptor ◽  
Interleukin 12 ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Scavenger Receptor A

ABSTRACT Alveolar macrophages are the effector cells largely responsible for clearance of Pneumocystis carinii from the lungs. Binding of organisms to β-glucan and mannose receptors has been shown to stimulate phagocytosis of the organisms. To further define the mechanisms used by alveolar macrophages for clearance of P. carinii, mice deficient in the expression of scavenger receptor A (SRA) were infected with P. carinii, and clearance of organisms was monitored over time. SRA-deficient (SRAKO) mice consistently cleared P. carinii faster than did wild-type control mice. Expedited clearance corresponded to elevated numbers of activated CD4+ T cells in the alveolar spaces of SRAKO mice compared to wild-type mice. Alveolar macrophages from SRAKO mice had increased expression of CD11b on their surfaces, consistent with an activated phenotype. However, they were not more phagocytic than macrophages expressing SRA, as measured by an in vivo phagocytosis assay. SRAKO alveolar macrophages produced significantly more tumor necrosis factor alpha (TNF-α) than wild-type macrophages when stimulated with lipopolysaccharide in vitro but less TNF-α in response to P. carinii in vitro. However, upon in vivo stimulation, SRAKO mice produced significantly more TNF-α, interleukin 12 (IL-12), and IL-18 in response to P. carinii infection than did wild-type mice. Together, these data indicate that SRA controls inflammatory cytokines produced by alveolar macrophages in the context of P. carinii infection.

Effect of recombinant Panton–Valentine leukocidin in vitro on apoptosis and cytokine production of human alveolar macrophages

2010 ◽  
Vol 56 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Benquan Wu ◽  
Wenxian Zhang ◽  
Jing Huang ◽  
Hui Liu ◽  
Tiantuo Zhang
Keyword(s):  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Lavage Fluid ◽  
Effector Cells ◽  
Tnf Α ◽  
Human Alveolar Macrophages ◽  
The Impact ◽  
Panton Valentine Leukocidin ◽  
Valentine Leukocidin

Panton–Valentine leukocidin (PVL) is associated with rare cases of necrotizing pneumonia that occur in otherwise healthy individuals. Human alveolar macrophages (HAMs) are major effector cells in host defense against infections. However, the impact of PVL on HAMs is uncertain. We evaluated the role of PVL in cytotoxicity and production of inflammatory cytokines secreted by HAMs. HAMs were purified from bronchoalveolar lavage fluid. Recombinant PVL (rPVL) was used in the study to interfere with HAM apoptosis and cytokine production in vitro. Hoechst 33342 fluorescence staining, transmission electron microscopy examination, and flow cytometry indicated that rPVL (10 nmol/L) treatment resulted in HAMs with markedly apoptotic characteristics, and HAMs treated with rPVL at 100 nmol/L showed clear indication of necrosis. A treatment of rPVL at 10 nmol/L elicited the secretion of IL-10 by HAMs relative to untreated control cells, but there was a slight decrease in the constitutive secretion of tumor necrosis factor (TNF)-α. Our results indicate that PVL-treated samples decreased HAM viability, leading to apoptosis at low concentrations and necrosis at high concentrations. In addition, PVL-treated cells released increased amounts of IL-10 and decreased amounts of TNF-α under apoptosis-inducing concentrations. Therefore, we speculated that PVL could play a negative role in HAM function at lower concentrations.

Long-Lasting Production of TGF-β1 by Alveolar Macrophages Exposed to Low Doses of Asbestos without Apoptosis

2007 ◽  
Vol 20 (4) ◽  
pp. 661-671 ◽  
Author(s):  
Y. Nishimura ◽  
T. Nishiike-Wada ◽  
Y. Wada ◽  
Y. Miura ◽  
T. Otsuki ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Tnf Α ◽  
Pulmonary Cells ◽  
Low Exposure ◽  
The Relationship ◽  
Tgf Β1

Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-α, which induces the production of TGF-β1, leading to lung fibrogenesis. The present study examines the production of TGF-β1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-β1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-α, IL-1β and IL-6 in the bronchoalveolar lavage fluid (B ALF) 1 day after the instillation, followed by increases in TGF-β1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-β1 in culture compared to those from the control rats. The addition of 2.5 μg/cm2 of CH augmented the production of TGF-β1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 μg/cm2 of CH, but was drastically induced at over 12.5 μg/cm2. In contrast, the production of TGF-β1 by AMs peaked at around 2.5 μg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-β1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-β1 may contribute not only to lung fibrosis but also to immune suppression.

scholarly journals Cholera Toxin Induces a Shift from Inactive to Active Cyclooxygenase 2 in Alveolar Macrophages Activated by Mycobacterium bovis BCG

2012 ◽  
Vol 81 (1) ◽  
pp. 373-380
Author(s):  
Mari Kogiso ◽  
Tsutomu Shinohara ◽  
C. Kathleen Dorey ◽  
Yoshimi Shibata
Keyword(s):  
Cholera Toxin ◽  
Mycobacterium Bovis ◽  
Alveolar Macrophages ◽  
Mucosal Vaccine ◽  
Prostaglandin E ◽  
Lung Cells ◽  
Cox 2 ◽  
Cox 1

Intranasal vaccination stimulates formation of cyclooxygenases (COX) and release of prostaglandin E2(PGE2) by lung cells, including alveolar macrophages. PGE2plays complex pro- or anti-inflammatory roles in facilitating mucosal immune responses, but the relative contributions of COX-1 and COX-2 remain unclear. Previously, we found thatMycobacterium bovisBCG, a human tuberculosis vaccine, stimulated increased release of PGE2by macrophages activatedin vitro; in contrast, intranasal BCG activated no PGE2release in the lungs, because COX-1 and COX-2 in alveolar macrophages were subcellularly dissociated from the nuclear envelope (NE) and catalytically inactive. This study tested the hypothesis that intranasal administration of BCG with cholera toxin (CT), a mucosal vaccine component, would shift the inactive, NE-dissociated COX-1/COX-2 to active, NE-associated forms. The results showed increased PGE2release in the lungs and NE-associated COX-2 in the majority of COX-2+macrophages. These COX-2+macrophages were the primary source of PGE2release in the lungs, since there was only slight enhancement of NE-associated COX-1 and there was no change in COX-1/COX-2 levels in alveolar epithelial cells following treatment with CT and/or BCG. To further understand the effect of CT, we investigated the timing of BCG versus CT administration forin vivoandin vitromacrophage activations. When CT followed BCG treatment, macrophagesin vitrohad elevated COX-2-mediated PGE2release, but macrophagesin vivoexhibited less activation of NE-associated COX-2. Our results indicate that inclusion of CT in the intranasal BCG vaccination enhances COX-2-mediated PGE2release by alveolar macrophages and further suggest that the effect of CTin vivois mediated by other lung cells.

Sign in / Sign up

Export Citation Format

Share Document