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.

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 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 In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19

2020 ◽  
Author(s):  
Clarissa S. Santoso ◽  
Zhaorong Li ◽  
Jaice T. Rottenberg ◽  
Xing Liu ◽  
Vivian X. Shen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Mononuclear Cells ◽  
Cytokine Production ◽  
Lavage Fluid ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Peripheral Blood Mononuclear ◽  
Approved Drugs ◽  
Fda Approved Drugs

AbstractTreatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

scholarly journals In vitro response of alveolar macrophages to infection with Coccidioides immitis

1980 ◽  
Vol 28 (2) ◽  
pp. 594-600
Author(s):  
L Beaman ◽  
C A Holmberg
Keyword(s):  
Macaca Mulatta ◽  
Alveolar Macrophages ◽  
Rhesus Macaques ◽  
Fungal Spores ◽  
Lavage Fluid ◽  
Immune Serum ◽  
Coccidioides Immitis ◽  
Bronchial Lavage ◽  
In Vitro Response

Alveolar macrophages obtained from rhesus macaques (Macaca mulatta) by bronchial lavage were observed to phagocytize endospores and arthrospores of Coccidioides immitis. When the macrophages were subsequently maintained in vitro, the phagocytized spores developed into spherules. There was no significant reduction in the viability of C. immitis after phagocytosis by macrophages from normal macaques, nor was killing induced by the addition of immune serum, complement, or lung lining material obtained from the bronchial lavage fluid. The inability of the macrophages to kill C. immitis may in part be explained by the observation that C. immitis appeared to inhibit fusion of the phagosomes containing the fungal spores with the lysosomes within the macrophages.

scholarly journals Lung Toxicity Analysis of Nano-Sized Kaolin and Bentonite: Missing Indications for a Common Grouping

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 204 ◽  
Author(s):  
Martin Wiemann ◽  
Antje Vennemann ◽  
Wendel Wohlleben
Keyword(s):  
Alveolar Macrophages ◽  
Binding Capacity ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Surfactant Protein ◽  
Hydrodynamic Diameter ◽  
Similar Chemical ◽  
Early Effects ◽  
Factor Α

Kaolin and bentonite (nanoclay NM-600) are nanostructured aluminosilicates that share a similar chemical composition, platelet-like morphology, and high binding capacity for biomolecules. To investigate if these material-based criteria allow for a common grouping, we prepared particle suspensions of kaolin and bentonite with a similar hydrodynamic diameter and administered them to NR8383 alveolar macrophages in vitro and also to a rat lung using quartz DQ12 as a reference material. Bentonite was far more bioactive in vitro, indicated by a lower threshold for the release of enzymes, tumor necrosis factor α, and H2O2. In addition, in the lung, the early effects of bentonite exceeded those of kaolin and even those of quartz, due to strongly increased numbers of inflammatory cells, and elevated concentrations of total protein and fibronectin within the bronchoalveolar lavage fluid. The pro-inflammatory effects of bentonite decreased over time, although assemblies of particle-laden alveolar macrophages (CD68 positive), numerous type-2 epithelial cells (immunopositive for pro-surfactant protein C), and hypertrophic lung epithelia persisted until day 21. At this point in time, kaolin-treated lungs were completely recovered, whereas quartz DQ12 had induced a progressive inflammation. We conclude that bentonite is far more bioactive than equally sized kaolin. This argues against a common grouping of aluminosilicates, previously suggested for different kaolin qualities.

Hyperoxia inhibits stimulated superoxide release by rat alveolar macrophages

1982 ◽  
Vol 53 (3) ◽  
pp. 685-689 ◽  
Author(s):  
H. J. Forman ◽  
J. J. Williams ◽  
J. Nelson ◽  
R. P. Daniele ◽  
A. B. Fisher
Keyword(s):  
Alveolar Macrophages ◽  
Polymorphonuclear Leukocytes ◽  
Cell Types ◽  
Lavage Fluid ◽  
Significant Decline ◽  
Specific Pathogen Free ◽  
Specific Pathogen ◽  
Cytochrome C Reduction

Factors responsible for the loss of respiratory burst capacity (stimulated extracellular O2-. release) of alveolar macrophages (AM) exposed to prolonged hyperoxia were assessed. Specific pathogen-free rats were exposed to 1 ATA O2 for 24–72 h, and lungs of survivors lavaged. Release of O2-. by cells after addition of concanavalin A, which stimulated AM but not polymorphonuclear leukocytes (PMN), or digitonin, which stimulated both cell types, was measured using cytochrome c reduction +/- superoxide dismutase. O2-. release by AM declined 47.2% (P less than 0.05) after 24 h of hyperoxia and 100% after 60 h. Percent PMN in the lavage was less than 3% at 0–36 h but increased to 16% at 48 h and to 44% at 72 h. Although addition of PMN to AM in vitro caused inhibition of AM O2-. release, the percent PMN required for inhibition was not reached in vivo until after a significant decline in AM O2-.-releasing capacity had already occurred. Cell-free lavage fluid from either control or hyperoxic rats did not affect AM O2-. release. AM in culture for 24 h in hyperoxia lost 76.7% (P less than 0.005) of O2-.-releasing capacity vs. cells incubated in 20% O2, although dye exclusion was unaffected. The results indicate that the major cause of loss of AM O2-. release by hyperoxia is a direct effect of O2 on the cells.

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.

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