Carbon nanotube instillation in mice causes sustained pulmonary inflammation and apoptosis of alveolar macrophages

Pneumologie ◽  
2011 ◽  
Vol 65 (12) ◽  
Author(s):  
NC Habel ◽  
S Hirn ◽  
F Tian ◽  
O Eickelberg ◽  
T Stoeger
Keyword(s):  
Carbon Nanotube ◽  
Alveolar Macrophages ◽  
Pulmonary Inflammation

Alveolar macrophages: novel therapeutic targets for respiratory diseases

2021 ◽  
Vol 23 ◽  
Author(s):  
Pamelia N. Lim ◽  
Maritza M. Cervantes ◽  
Linh K. Pham ◽  
Alissa C. Rothchild
Keyword(s):  
Alveolar Macrophages ◽  
Respiratory Diseases ◽  
Severe Disease ◽  
Pulmonary Inflammation ◽  
Therapeutic Targets ◽  
Therapeutic Strategies ◽  
Lung Damage ◽  
Respiratory Pathogens ◽  
Inhaled Antibiotics ◽  
Potential Risks

Abstract Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease

2003 ◽  
Vol 284 (3) ◽  
pp. L518-L525 ◽  
Author(s):  
Machiko Ikegami ◽  
Rajwinder Dhami ◽  
Edward H. Schuchman
Keyword(s):  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Acid Sphingomyelinase ◽  
Deficient Mouse ◽  
Niemann Pick Disease ◽  
Surfactant Inhibition ◽  
Niemann Pick ◽  
Surfactant Composition ◽  
Pick Disease

Types A and B Niemann-Pick disease (NPD) are lipid storage disorders caused by the deficient activity of acid sphingomyelinase (ASM). In humans, NPD is associated with the dysfunction of numerous organs including the lung. Gene targeting of the ASM gene in transgenic mice produced an animal model with features typical of NPD, including pulmonary inflammation. To assess mechanisms by which ASM perturbed lung function, we studied lung morphology, surfactant content, and metabolism in ASM-deficient mice in vivo. Pulmonary inflammation, with increased cellular infiltrates and the accumulation of alveolar material, was associated with alterations in surfactant content. Saturated phosphatidylcholine (SatPC) content was increased twofold, and sphingomyelin content was increased 5.5-fold in lungs of the ASM knockout (ASMKO) mice. Additional sphingomyelin enhanced the sensitivity of surfactant inhibition by plasma proteins. Clearance of SatPC from the lungs of ASMKO mice was decreased. Catabolism of SatPC by alveolar macrophages from the ASMKO mouse was significantly decreased, likely accounting for decreased pulmonary SatPC in vivo. In summary, ASM is required for normal surfactant catabolism by alveolar macrophages in vivo. Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse.

scholarly journals Activated alveolar macrophages in subclinical pulmonary inflammation in collagen vascular diseases.

Thorax ◽  
1988 ◽  
Vol 43 (1) ◽  
pp. 24-30 ◽  
Author(s):  
B Wallaert ◽  
F Bart ◽  
C Aerts ◽  
A Ouaissi ◽  
P Y Hatron ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Vascular Diseases ◽  
Collagen Vascular Diseases

scholarly journals Analysis of Immune Responses in Acinetobacter baumannii-Infected Klotho Knockout Mice: A Mouse Model of Acinetobacter baumannii Infection in Aged Hosts

2020 ◽  
Vol 11 ◽  
Author(s):  
Yoshinori Sato ◽  
Shigeru Tansho-Nagakawa ◽  
Tsuneyuki Ubagai ◽  
Yasuo Ono
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Acinetobacter Baumannii ◽  
Alveolar Macrophages ◽  
Post Infection ◽  
Pulmonary Inflammation ◽  
Cell Subset ◽  
Dendritic Cell Subset ◽  
Immune Functions ◽  
Cd11b Expression

Acinetobacter baumannii is an important opportunistic pathogen that primarily afflicts elderly people. To clarify the pathogenicity of A. baumannii in the elderly, we investigated immune responses to A. baumannii ATCC 19606 infection in klotho knockout (KO) mice, the mouse model of aging. Following intravenous inoculation, the mice seldom displayed severe symptoms. However, the survival rate was 56% at 7 days post-infection. Bacteria were detected in the lungs of klotho KO mice but not klotho wildtype (WT) mice at 7 days post-infection. Neutrophils, eosinophils, interstitial macrophages, and monocyte/dendritic cell subset in the lungs of klotho KO mice were transiently induced after infection with A. baumannii. The number of alveolar macrophages in klotho KO mice was lower than that in klotho WT mice, except for 1 day post-infection. CD11b expression on neutrophils and alveolar macrophages in the lungs of klotho KO mice was seldom upregulated by the infection. These results suggested that immune functions eliminating bacteria in the lungs of klotho KO mice were insufficient. CD11blow conventional DC cells hardly increased in klotho KO mice infected with A. baumannii. Additionally, the production of interleukin (IL)-10 in the sera of klotho KO mice was significantly higher than that in klotho WT mice, whereas that production of interferon-gamma was not detected in the sera of klotho KO mice. These results suggested that acquired immune responses were hardly induced in klotho KO mice. IL-1β, CXCL1, CXCL2, and CCL2 expression was significantly higher in the lungs of klotho KO mice infected with A. baumannii than in those of klotho WT mice at 1 day post-infection. These results suggested that pulmonary inflammation was elicited in klotho KO mice during early infection. The expression levels of proinflammatory cytokines significantly correlated with TLR9 expression in the lungs of klotho KO mice. The collective results demonstrate an A. baumannii infection state in aged hosts and suggest that pulmonary inflammation and bacterial burden should be noted in aged hosts even in the absence of severe symptoms of A. baumannii infection.

scholarly journals Platelets instruct T reg cells and macrophages in the resolution of lung inflammation

2021 ◽  
Vol 218 (7) ◽  
Author(s):  
Rick Kapur ◽  
John W. Semple
Keyword(s):  
Alveolar Macrophages ◽  
Lung Inflammation ◽  
Potential Role ◽  
Pulmonary Inflammation ◽  
Immune Functions ◽  
Inflammatory Phenotype ◽  
Anti Inflammatory

Platelets convey important nonhemostatic immune functions; however, their potential role in resolving pulmonary inflammation remains to be determined. In this issue of JEM, Rossaint et al. (2021. J. Exp. Med. https://doi.org/10.1084/jem.20201353) reveal that platelets contribute to the resolution of pulmonary inflammation by directly recruiting T regulatory (T reg) cells to the lungs and by transcriptionally reprogramming alveolar macrophages toward an anti-inflammatory phenotype.

scholarly journals Interleukin 17 Receptor E (IL-17RE) and IL-17C Mediate the Recruitment of Neutrophils during Acute Streptococcus pneumoniae Pneumonia

2019 ◽  
Vol 87 (11) ◽  
Author(s):  
Patrick Steck ◽  
Felix Ritzmann ◽  
Anja Honecker ◽  
Giovanna Vella ◽  
Christian Herr ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Alveolar Macrophages ◽  
Pulmonary Inflammation ◽  
Interleukin 17 ◽  
Immune Functions ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Tnf Α ◽  
Factor Alpha ◽  
Functional Receptor

ABSTRACT Neutrophils contribute to lung injury in acute pneumococcal pneumonia. The interleukin 17 receptor E (IL-17RE) is the functional receptor for the epithelial-derived cytokine IL-17C, which is known to mediate innate immune functions. The aim of this study was to investigate the contribution of IL-17RE/IL-17C to pulmonary inflammation in a mouse model of acute Streptococcus pneumoniae pneumonia. Numbers of neutrophils and the expression levels of the cytokine granulocyte colony-stimulating factor (G-CSF) and tumor necrosis factor alpha (TNF-α) were decreased in lungs of IL-17RE-deficient (Il-17re−/−) mice infected with S. pneumoniae. Numbers of alveolar macrophages rapidly declined in both wild-type (WT) and Il-17re−/− mice and recovered 72 h after infection. There were no clear differences in the elimination of bacteria and numbers of blood granulocytes between infected WT and Il-17re−/− mice. The fractions of granulocyte-monocyte progenitors (GMPs) were significantly reduced in infected Il-17re−/− mice. Numbers of neutrophils were significantly reduced in lungs of mice deficient for IL-17C 24 h after infection with S. pneumoniae. These data indicate that the IL-17C/IL-17RE axis promotes the recruitment of neutrophils without affecting the recovery of alveolar macrophages in the acute phase of S. pneumoniae lung infection.

scholarly journals Cardamonin attenuates phorbol 12-myristate 13-acetate-induced pulmonary inflammation in alveolar macrophages

2021 ◽  
pp. 112761
Author(s):  
Yen-Chang Chen ◽  
Yu-Kai Cheng ◽  
Jia-Hong Chen ◽  
Cheng-Fang Tsai ◽  
Tsung-Kai Wang ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Pulmonary Inflammation

scholarly journals IL-10 and class 1 histone deacetylases act synergistically and independently on the secretion of proinflammatory mediators in alveolar macrophages

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245169
Author(s):  
Brent A. Stanfield ◽  
Todd Purves ◽  
Scott Palmer ◽  
Bruce Sullenger ◽  
Karen Welty-Wolf ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Histone Deacetylases ◽  
Pulmonary Inflammation ◽  
Protein Synthesis Inhibitor ◽  
Dependent Manner ◽  
Synthesis Inhibitor ◽  
Proinflammatory Mediators ◽  
Chemokine Signaling ◽  
Class 1 ◽  
Anti Inflammatory

Introduction Anti-inflammatory cytokine IL-10 suppresses pro-inflammatory IL-12b expression after Lipopolysaccharide (LPS) stimulation in colonic macrophages, as part of the innate immunity Toll-Like Receptor (TLR)-NF-κB activation system. This homeostatic mechanism limits excess inflammation in the intestinal mucosa, as it constantly interacts with the gut flora. This effect is reversed with Histone Deacetylase 3 (HDAC3), a class I HDAC, siRNA, suggesting it is mediated through HDAC3. Given alveolar macrophages’ prominent role in Acute Lung Injury (ALI), we aim to determine whether a similar regulatory mechanism exists in the typically sterile pulmonary microenvironment. Methods Levels of mRNA and protein for IL-10, and IL-12b were determined by qPCR and ELISA/Western Blot respectively in naïve and LPS-stimulated alveolar macrophages. Expression of the NF-κB intermediaries was also similarly assessed. Experiments were repeated with AS101 (an IL-10 protein synthesis inhibitor), MS-275 (a selective class 1 HDAC inhibitor), or both. Results LPS stimulation upregulated all proinflammatory mediators assayed in this study. In the presence of LPS, inhibition of IL-10 and/or class 1 HDACs resulted in both synergistic and independent effects on these signaling molecules. Quantitative reverse-transcriptase PCR on key components of the TLR4 signaling cascade demonstrated significant diversity in IL-10 and related gene expression in the presence of LPS. Inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the transcription of MyD88, IRAK1, Rela and the NF-κB p50 subunit. Interestingly, by quantitative ELISA inhibition of IL-10 secretion and/or class 1 HDACs in the presence of LPS independently affected the secretion of not only IL-10, IL-12b, and TNFα, but also proinflammatory mediators CXCL2, IL-6, and MIF. These results suggest that IL-10 and class 1 HDAC activity regulate both independent and synergistic mechanisms of proinflammatory cytokine/chemokine signaling. Conclusions Alveolar macrophages after inflammatory stimulation upregulate both IL-10 and IL-12b production, in a highly class 1 HDAC-dependent manner. Class 1 HDACs appear to help maintain the balance between the pro- and anti-inflammatory IL-12b and IL-10 respectively. Class 1 HDACs may be considered as targets for the macrophage-initiated pulmonary inflammation in ALI in a preclinical setting.

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