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.

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

scholarly journals Respiratory pathogens in a febrile cohort from Tanzania and associated risks for severe disease outcome

2020 ◽  
Vol 101 ◽  
pp. 367
Author(s):  
Y. Zhuang ◽  
M.K.Y. Mah ◽  
Y. Chen ◽  
J.A. Crump ◽  
M. Carugati ◽  
...  
Keyword(s):  
Severe Disease ◽  
Disease Outcome ◽  
Respiratory Pathogens

scholarly journals Current therapeutic strategies for respiratory diseases using mesenchymal stem cells

MedComm ◽  
2021 ◽  
Author(s):  
Ming‐yao Wang ◽  
Ting‐yue Zhou ◽  
Zhi‐dong Zhang ◽  
Hao‐yang Liu ◽  
Zhi‐yao Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Respiratory Diseases ◽  
Therapeutic Strategies

Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection

2002 ◽  
Vol 282 (3) ◽  
pp. L563-L572 ◽  
Author(s):  
Ann Marie LeVine ◽  
Kevan Hartshorn ◽  
James Elliott ◽  
Jeffrey Whitsett ◽  
Thomas Korfhagen
Keyword(s):  
Lung Inflammation ◽  
Influenza A ◽  
Influenza Infection ◽  
Pulmonary Inflammation ◽  
Defense Responses ◽  
Interferon Γ ◽  
Viral Clearance ◽  
Myeloperoxidase Activity ◽  
Respiratory Pathogens ◽  
Innate Defense

Mice lacking surfactant protein SP-A [SP-A(−/−)] and wild type SP-A(+/+) mice were infected with influenza A virus (IAV) by intranasal instillation. Decreased clearance of IAV was observed in SP-A(−/−) mice and was associated with increased pulmonary inflammation. Treatment of SP-A(−/−) mice with exogenous SP-A enhanced viral clearance and decreased lung inflammation. Uptake of IAV by alveolar macrophages was similar in SP-A(−/−) and SP-A(+/+) mice. Myeloperoxidase activity was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(−/−) mice. B lymphocytes and activated T lymphocytes were increased in the lung and spleen, whereas T helper (Th) 1 responses were increased [interferon-γ, interleukin (IL)-2, and IgG2a] and Th2 responses were decreased (IL-4, and IL-10, and IgG1) in the lungs of SP-A(−/−) mice 7 days after IAV infection. In the absence of SP-A, impaired viral clearance was associated with increased lung inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1 responses. Because the airway is the usual portal of entry for IAV and other respiratory pathogens, SP-A is likely to play a role in innate defense and adaptive immune responses to IAV.

scholarly journals Different Therapeutic Strategies to Tackle the Infection Associated with COVID-19

2021 ◽  
Author(s):  
Meemansha Sharma ◽  
Thakur Uttam Singh ◽  
Madhu Cholenahalli Lingaraju ◽  
Subhashree Parida
Keyword(s):  
Human Resources ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Therapeutic Strategies ◽  
Morbidity And Mortality ◽  
The Novel ◽  
Present Book ◽  
Short Period

Covid-19 is a pandemic and the whole world is facing the loss in terms of morbidity and mortality of the human resources. Therefore, there is an urgent need for various therapeutic agents or drugs to treat the covid-19 patients. Although, vaccination process is under way, it is not possible to provide the vaccination to whole world in a short period. Therefore, it is an essential strategy to work on the various therapeutic aspects of covid-19 treatment. The present book chapter will discuss and review the various aspects of the treatment strategies of the covid-19. Further, we will provide an overview of the virus and host based potential therapeutic targets along with existing therapeutics which are effective against SARS-CoV-2 virus. Also, the novel vaccines are being developed against covid-19 deadly virus will be discussed.

Eosinopenie als Biomarker des Schweregrads einer COVID-19-Infektion

2021 ◽  
pp. 1-2
Author(s):  
Panagiota Xanthouli
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Disease Severity ◽  
Respiratory Diseases ◽  
Severe Disease ◽  
Public Hospitals ◽  
Chronic Respiratory Diseases ◽  
Lack Of Information ◽  
Obstructive Sleep ◽  
Increased Risk

<b>Background:</b> Studies on the role of eosinophils in coronavirus disease 2019 (COVID-19) are scarce, though available findings suggest a possible association with disease severity. Our study analyzes the relationship between eosinophils and COVID-19, with a focus on disease severity and patients with underlying chronic respiratory diseases. <b>Methods:</b> We performed a retrospective analysis of 3,018 subjects attended at two public hospitals in Madrid (Spain) with PCR-confirmed SARS-CoV-2 infection from January 31 to April 17, 2020. Patients with eosinophil counts less than 0.02 × 10<sup>9</sup>/L were considered to have eosinopenia. Individuals with chronic respiratory diseases (<i>n</i> = 384) were classified according to their particular underlying condition, i.e., asthma, chronic pulmonary obstructive disease, or obstructive sleep apnea. <b>Results:</b> Of the 3018 patients enrolled, 479 were excluded because of lack of information at the time of admission. Of 2539 subjects assessed, 1,396 patients presented an eosinophil count performed on admission, revealing eosinopenia in 376 cases (26.93%). Eosinopenia on admission was associated with a higher risk of intensive care unit (ICU) or respiratory intensive care unit (RICU) admission (OR:2.21; 95% CI:1.42–3.45; <i>p</i> &#x3c; 0.001) but no increased risk of mortality (<i>p</i> &#x3e; 0.05). <b>Conclusion:</b> Eosinopenia on admission conferred a higher risk of severe disease (requiring ICU/RICU care), but was not associated with increased mortality. In patients with chronic respiratory diseases who develop COVID-19, age seems to be the main risk factor for progression to severe disease or death.

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 Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 114
Author(s):  
Lisa Linck-Paulus ◽  
Claus Hellerbrand ◽  
Anja K. Bosserhoff ◽  
Peter Dietrich
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
The Future ◽  
Associated Proteins ◽  
Cancer Types ◽  
Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

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 G-CSF maintains controlled neutrophil mobilization during acute inflammation by negatively regulating CXCR2 signaling

2016 ◽  
Vol 213 (10) ◽  
pp. 1999-2018 ◽  
Author(s):  
Besnik Bajrami ◽  
Haiyan Zhu ◽  
Hyun-Jeong Kwak ◽  
Subhanjan Mondal ◽  
Qingming Hou ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Acute Inflammation ◽  
Early Stage ◽  
Pulmonary Inflammation ◽  
Lung Damage ◽  
Critical Event ◽  
Neutrophil Accumulation ◽  
Peripheral Blood Neutrophil ◽  
Lung Injury Model

Cytokine-induced neutrophil mobilization from the bone marrow to circulation is a critical event in acute inflammation, but how it is accurately controlled remains poorly understood. In this study, we report that CXCR2 ligands are responsible for rapid neutrophil mobilization during early-stage acute inflammation. Nevertheless, although serum CXCR2 ligand concentrations increased during inflammation, neutrophil mobilization slowed after an initial acute fast phase, suggesting a suppression of neutrophil response to CXCR2 ligands after the acute phase. We demonstrate that granulocyte colony-stimulating factor (G-CSF), usually considered a prototypical neutrophil-mobilizing cytokine, was expressed later in the acute inflammatory response and unexpectedly impeded CXCR2-induced neutrophil mobilization by negatively regulating CXCR2-mediated intracellular signaling. Blocking G-CSF in vivo paradoxically elevated peripheral blood neutrophil counts in mice injected intraperitoneally with Escherichia coli and sequestered large numbers of neutrophils in the lungs, leading to sterile pulmonary inflammation. In a lipopolysaccharide-induced acute lung injury model, the homeostatic imbalance caused by G-CSF blockade enhanced neutrophil accumulation, edema, and inflammation in the lungs and ultimately led to significant lung damage. Thus, physiologically produced G-CSF not only acts as a neutrophil mobilizer at the relatively late stage of acute inflammation, but also prevents exaggerated neutrophil mobilization and the associated inflammation-induced tissue damage during early-phase infection and inflammation.

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