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.

scholarly journals Exogenous Heat-Killed Escherichia coli Improves Alveolar Macrophage Activity and Reduces Pneumocystis carinii Lung Burden in Infant Mice

2007 ◽  
Vol 75 (7) ◽  
pp. 3382-3393 ◽  
Author(s):  
Kerry M. Empey ◽  
Melissa Hollifield ◽  
Beth A. Garvy
Keyword(s):  
Escherichia Coli ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Pneumocystis Carinii ◽  
Effector Cells ◽  
Macrophage Activity ◽  
Adult Mice

ABSTRACT Pneumocystis carinii is an opportunistic fungal pathogen that causes life-threatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to Pneumocystis pulmonary infections. We have previously demonstrated that there is approximately a 3-week delay in the clearance of Pneumocystis organisms from pup mouse lungs compared to that in adults. We have further shown that there is approximately a 1-week delay in alveolar macrophage activation in pups versus adult mice. Alveolar macrophages are the primary effector cells responsible for the killing and clearance of Pneumocystis, suggesting that pup alveolar macrophages may be involved in the delayed clearance of this organism. Alveolar macrophages cultured in vitro with Pneumocystis alone demonstrate little to no activation, as indicated by a lack of cytokine production. However, when cultured with lipopolysaccharide (LPS) or zymosan, cytokine production was markedly increased, suggesting that pup alveolar macrophages are specifically unresponsive to Pneumocystis organisms rather than being intrinsically unable to become activated. Furthermore, pup mice treated with aerosolized, heat-killed Escherichia coli in vivo were able to clear Pneumocystis more efficiently than were control mice. Together, these data suggest that while pup alveolar macrophages are unresponsive to P. carinii f. sp. muris organisms, they are capable of activation by heat-killed E. coli in vivo, as well as LPS and zymosan in vitro. The lack of response of pup mice to P. carinii f. sp. muris may reflect protective mechanisms specific to the developing pup lung, but ultimately it results in insufficient clearance of Pneumocystis organisms.

scholarly journals Surfactant Proteins A/D–CD14 on Alveolar Macrophages Is a Common Pathway Associated With Phagocytosis of Nanomaterials and Cytokine Production

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiqi Wang ◽  
Qiong Wang ◽  
Ziyue Zhao ◽  
Jingbo Fan ◽  
Linghan Qin ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Lavage Fluid ◽  
Surfactant Proteins ◽  
Chemical Compositions ◽  
Common Pathway ◽  
Airborne Dust ◽  
Pulmonary Exposure ◽  
Associated Proteins

Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production, and to determine whether a common pathway for phagocytosis of ENMs with different properties exists. For these purposes, four ENMs, MWCNT-7, TiO2, SiO2, and fullerene C60, with different shapes, sizes, chemical compositions, and surface reactivities, were chosen for this study. Short-term pulmonary exposure to MWCNT-7, TiO2, SiO2, and C60 induced inflammation in the rat lung, and most of the administered ENMs were phagocytosed by alveolar macrophages. The ENMs were phagocytosed by isolated primary alveolar macrophages (PAMs) in vitro, and phagocytosis was enhanced by rat bronchioalveolar lavage fluid (BALF), suggesting that proteins in the BALF were associated with phagocytosis. Analysis of proteins bound to the 4 ENMs by LC/MS indicated that surfactant-associated proteins A and D (SP-A, SP-D) were common binding proteins for all the 4 ENMs. Both BALF and SP-A, but not SP-D, enhanced TNF-α production by MWCNT-7 treated PAMs; BALF, SP-A, and SP-D increased IL-1β production in TiO2 and SiO2 treated PAMs; and BALF, SP-A, and SP-D enhanced IL-6 production in C60 treated PAMs. Knockdown of CD14, a receptor for SP-A/D, significantly reduced phagocytosis of ENMs and SP-A-enhanced cytokine production by PAMs. These results indicate that SP-A/D can opsonize all the test ENMs and enhance phagocytosis of the ENMs by alveolar macrophages through CD14, suggesting that SP-A/D-CD14 is a common pathway mediating phagocytosis of ENMs. Cytokine production induced by ENMs, however, is dependent on the type of ENM that is phagocytosed. Our results demonstrate a dual role for surfactant proteins as opsonins for both microbes and for inhaled dusts and fibers, including ENMs, allowing macrophages to recognize and remove the vast majority of these particles, thereby, greatly lessening their toxicity in the lung.

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.

Expression and modulation of ICAM-1, TNF-α and RANTES in human alveolar macrophages from lung-transplant recipients in vitro

1998 ◽  
Vol 6 (3) ◽  
pp. 183-192 ◽  
Author(s):  
Michèle Fattal-German ◽  
François Le Roy Ladurie ◽  
Jacques Cerrina ◽  
Florence Lecerf ◽  
Sonia Berrih-Aknin
Keyword(s):  
Alveolar Macrophages ◽  
Lung Transplant ◽  
Transplant Recipients ◽  
Tnf Α ◽  
Human Alveolar Macrophages ◽  
Lung Transplant Recipients

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.

scholarly journals Surfactant protein A /D-CD14 is Associated with Phagocytosis of Nanomaterials and Cytokine Production by Alveolar Macrophages

2021 ◽  
Author(s):  
Jiegou Xu ◽  
Qiqi Wang ◽  
Qiong Wang ◽  
Ziyue Zhao ◽  
Jingbo Fan ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Protein A ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Surface Reactivity ◽  
Common Pathway ◽  
Airborne Dust ◽  
Associated Proteins

Abstract Background: Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production and to find out a common pathway for ENMs with different properties. Results: 4 ENMs including MWCNT-7, TIO2, SIO2, and fullerene C60, each with different shape, size, chemical composition and surface reactivity, were chosen for the study. Short-term pulmonary exposure of MWCNT-7, TIO2, SIO2, and C60 induced inflammation in the rat lung, and most of the administered ENMs were phagocytosed by alveolar macrophages. The ENMs were phagocytosed by isolated primary alveolar macrophages (PAMs) in vitro, which was enhanced by the rat bronchioalveolar lavage fluid (BALF), suggesting that proteins in BALF were associated with the phagocytosis. Further analysis of the 4 ENMs-bound proteins by LC/MS indicated that surfactant-associated proteins A and D (SP-A, SP-D) were common binding proteins for all the 4 ENMs. Like BALF, SP-A, but not SP-D, enhanced TNF-a production in the MWCNT-7-treated PAMs; both SP-A and SP-D increased IL-b production in the TIO2-or SIO2-stimulated PAMs; while SP-A and SP-D enhanced IL-6 production in the C60-stimulated PAMs. Knockdown of CD14, a receptor for SP-A/D, significantly reduced the cytokine production and ENMs phagocytosis. Conclusions: These results indicate that SP-A/D can opsonize all the studied ENMs to enhance phagocytosis of the ENMs by alveolar macrophages through CD14, suggesting that SP-A/D-CD14 is a common pathway mediating phagocytosis of ENMs. Cytokine production induced by ENMs, however, is dependent on what an ENM is phagocytosed. Our results are helpful for the understanding of clearance of ENMs by alveolar macrophages and mechanisms of different ENMs-induced lung toxicity.

Effect of Sulfur Dioxide on Cytokine Production of Human Alveolar Macrophages in Vitro

1996 ◽  
Vol 51 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Marli Maria Knorst ◽  
Klaus Kienast ◽  
Joachim Müller-Quernheim ◽  
Rudolf Ferlinz
Keyword(s):  
Sulfur Dioxide ◽  
Alveolar Macrophages ◽  
Cytokine Production ◽  
Human Alveolar Macrophages

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals PSIII-38 Butyric acid and derivatives: In vitro anti-inflammatory effects tested in porcine alveolar macrophages

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 370-370
Author(s):  
Lauren L Kovanda ◽  
Monika Hejna ◽  
Yanhong Liu
Keyword(s):  
Organic Acid ◽  
Butyric Acid ◽  
Sodium Butyrate ◽  
Alveolar Macrophages ◽  
Block Design ◽  
Lps Challenge ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Challenge Group

Abstract The aim of this experiment was to examine the anti-inflammatory effects of butyric acid, sodium butyrate, monobutyrin and tributyrin using porcine alveolar macrophages (PAMs). PAMs were isolated from the bronchial lavage of 6 piglets at 6 weeks of age, and then seeded at 106 cells/mL in 24-well plates. After 24 h incubation, cells were treated with different treatments in a randomized complete block design with 10 replicates. The treatments were in a factorial arrangement with 2 doses of lipopolysaccharide (LPS, 0 or 1 μg/mL) and 5 levels of organic acid (0, 0.5, 1, 2, 4 mM for butyric acid and tributyrin and 0, 1, 2, 4, 8 mM for sodium butyrate and monobutyrin). Supernatants were collected after another 24 h incubation and analyzed for tumor necrosis factor alpha (TNF-α). Cell viability was also tested by the MTT assay. Data were analyzed using the MIXED procedure of SAS. No cytotoxic effect was observed in LPS challenge and each organic acid with the percentage of live cells was more than 76% in comparison to the sham control. Sodium butyrate at 2 and 4 mM dose exhibited (P < 0.01) a stimulatory effect on cell proliferation. LPS challenge remarkably stimulated (P < 0.0001) TNF-α secretion from PAMs. In the non-challenge group, butyric acid, monobutyrin, and tributyrin linearly reduced TNF-α production from PAMs, whereas 2 mM sodium butyrate tended to increase (P = 0.056) TNF-α secretion from PAMs. In the LPS challenge group, all tested organic acid dose-dependently reduced (P < 0.001) TNF-α production from LPS-challenged PAMs, with the strongest inhibiting effect observed at the highest dose. Results indicated that butyric acid and its derivatives that were tested in the current experiment all had strong anti-inflammatory activities in vitro.

Sign in / Sign up

Export Citation Format

Share Document