Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Hetzel, Miriam; Ackermann, Mania; Lachmann, Nico

doi:10.3390/ijms22073308

Cited by 31 publications

(27 citation statements)

References 163 publications

(202 reference statements)

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“…They derive from prenatal monocytes, self-renew, and have shown remarkable plasticity by altering their transcriptome in response to the environmental changes (3,(5)(6)(7)(8). Their transcriptional profile is altered in various inflammatory lung diseases, including asthma (2,9), chronic obstructive pulmonary disease (10), cystic fibrosis (CF) (11), and cancer (12)(13)(14)(15)(16)(17). Therefore, enhancing our current understanding of the normal cellular composition and functional diversity of AM subtypes will help characterize disease-related transcriptional changes more precisely and assess targeting specifically a given AM subtype to restore immune balance.…”

Section: Introductionmentioning

confidence: 99%

ScRNA-seq Expression ofIFI27andAPOC2Identifies Four Alveolar Macrophage Superclusters in Healthy BALF

Kolling

Aridgides

et al. 2022

Preprint

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Rationale: Alveolar macrophages (AMs) reside on the luminal surface of the airways and alveoli, ensuring proper gas exchange by ingesting cellular debris and pathogens, and regulating inflammatory responses. Recent studies have highlighted the heterogeneity of airspace macrophages from healthy bronchoalveolar lavage fluid and cystic fibrosis sputum. Understanding the heterogeneity and diverse roles played by AMs and recruited monocytes is critical for treating CF and other airway diseases. Objectives: To identify and compare the cellular composition and functional diversity between CF and healthy airspace macrophages and monocytes. Methods: We performed single-cell RNA sequencing (scRNA-seq) on 113,213 BAL cells from four healthy and three mild CF subjects. Transcriptional data and TotalSeq technology were used to confirm cell surface markers that distinguish resident AMs from recruited monocytes. Measurements and Main Results: Unbiased clustering identified four AM superclusters based on the expression of APOC2 and IFI27 genes. Each supercluster contains four shared subclusters named after their differentially expressed gene(s): IGF1.AMs, CCL18.AMs, CXCL5.AMs, and Cholesterol.AMs. AM Supercluster 4 contained two additional subclusters. Beyond the superclusters, several additional AM clusters were identified: Chemokine, Metallothionein, Interferon, and Cycling AMs. Interestingly, the Chemokine cluster further divides into four subclusters, each selectively expressing a unique combination of chemokines. Lastly, minimal differences were observed between mild CF and healthy individuals in airspace cellular composition. Conclusions: ScRNA-seq identified four AM superclusters. Several fundamental questions require further investigation, including these clusters locations, functions, transcription factors that regulate their distinct programming, and whether similar macrophage superclusters can be found in other organs.

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Section: Introductionmentioning

confidence: 99%

ScRNA-seq Expression ofIFI27andAPOC2Identifies Four Alveolar Macrophage Superclusters in Healthy BALF

Kolling

Aridgides

et al. 2022

Preprint

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“…Many more drug targeting options are associated specific proteins, protein receptors, mRNA, specific biochemical pathways and cells, e.g., macrophages and platelets, which may play a critical role in the proliferation of SARS-CoV-2, as well as the outcome of the COVID-19 infection [69,84,85]. Furthermore, drug targeting strategies may involve the activity of proteomic, genomic, transcription and other factors associated with the mRNA and proteins of the virus and host cell (Table 1) [86][87][88][89][90][91][92][93].…”

Section: Drug Targeting Based Theory and Methods Against Sars-cov-2mentioning

confidence: 99%

The need for a multi-level drug targeting strategy to curb the COVID-19 pandemic

Kontoghiorghes¹,

Fetta²,

Kontoghiorghe³

2021

Front. Biosci. (Landmark Ed)

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Introduction 3. The effects of vaccines on the COVID-19 pandemic 4. Drug based concepts for the prevention of COVID-19 4.1 Factors contributing to variable susceptibility to SARS-CoV-2 infection 4.2 Drug based examples of prevention targets against COVID-19 infection 5. Drug targeting based theory and methods against SARS-CoV-2 6. Examples of drugs that are widely used in COVID-19 patients 7. Examples of drugs that could be used in COVID-19 8. Pharmacological and toxicological aspects of drugs against COVID-19 9. New developments affecting multi-level drug targeting strategies against COVID-19 10. Conclusions 11. Author contributions 12. Ethics approval and consent to participate 13. Acknowledgment 14. Funding 15. Conflict of interest 16. References Abbreviations: ACE2, angiotensin converting enzyme 2; ARDS, acute respiratory distress syndrome; EMA, European medicines agency; FDA, food and drug admin-istration; FIASMA, inhibitors of acid sphingomyelinase; GM-CSF, granulocyte-macrophage colony-stimulating fac-tor; COVID-19, coronavirus disease 2019; IL, interleukin, e.g., IL-1, IL-6, IL-8; iv, intravenous; IND, investigational new drugs; LDH, lactate dehydrogenase; LMWH, low molecular weight heparin; MERS-CoV, Middle East Respiratory Syndrome coronavirus; p.o., oral administration; QALY, quality-adjusted life years; SARS-CoV-1, severe acute respiratory syndrome coronavirus 1; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; sc, sub-cutaneous; TMPRSS2, transmembrane protease serine 2; WHO, world health organization.

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“…Under normal conditions, ferritinophagy involves the sequestration of ferritin into autophagosomes and its delivery to lysosomes for degradation. Different factors influencing the process of autophagy and lysosomal degradation can also affect ferritinophagy and ferroptosis [ 113 , 114 , 115 , 116 ]. Ferroptotic cell death is evident in many clinical conditions including cardiac and multi-organ damage in COVID-19 [ 117 , 118 , 119 ].…”

Section: Deferiprone Targeting Molecules and Metabolic Pathways Of Co...mentioning

confidence: 99%

Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology

Kontoghiorghes¹

2022

IJMS

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The need for preparing new strategies for the design of emergency drug therapies against COVID-19 and similar diseases in the future is rather urgent, considering the high rate of morbidity and especially mortality associated with COVID-19, which so far has exceeded 18 million lives. Such strategies could be conceived by targeting the causes and also the serious toxic side effects of the diseases, as well as associated biochemical and physiological pathways. Deferiprone (L1) is an EMA- and FDA-approved drug used worldwide for the treatment of iron overload and also other conditions where there are no effective treatments. The multi-potent effects and high safety record of L1 in iron loaded and non-iron loaded categories of patients suggests that L1 could be developed as a “magic bullet” drug against COVID-19 and diseases of similar symptomatology. The mode of action of L1 includes antiviral, antimicrobial, antioxidant, anti-hypoxic and anti-ferroptotic effects, iron buffering interactions with transferrin, iron mobilizing effects from ferritin, macrophages and other cells involved in the immune response and hyperinflammation, as well as many other therapeutic interventions. Similarly, several pharmacological and other characteristics of L1, including extensive tissue distribution and low cost of production, increase the prospect of worldwide availability, as well as many other therapeutic approach strategies involving drug combinations, adjuvant therapies and disease prevention.

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Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Cited by 31 publications

References 163 publications

ScRNA-seq Expression ofIFI27andAPOC2Identifies Four Alveolar Macrophage Superclusters in Healthy BALF

ScRNA-seq Expression ofIFI27andAPOC2Identifies Four Alveolar Macrophage Superclusters in Healthy BALF

The need for a multi-level drug targeting strategy to curb the COVID-19 pandemic

Deferiprone: A Forty-Year-Old Multi-Targeting Drug with Possible Activity against COVID-19 and Diseases of Similar Symptomatology

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