GM-CSF in inflammation

Hamilton, John A.

doi:10.1084/jem.20190945

Cited by 202 publications

(207 citation statements)

References 221 publications

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“…Activin A and other proteins encoded by several GM-CSF-associated gene markers, including MMP12 and CCR2, have been also detected in macrophages from active RA joints [17][18][19]. GM-CSF induces macrophage differentiation and survival from hematopoietic progenitor cells [31,35]. In contrast to M-CSF, GM-CSF is undetectable in the systemic circulation during homeostasis but is produced and active at sites of tissue in ammation, and is a key driver of tissue in ammation and arthritic pain [36,37].…”

Section: Discussionmentioning

confidence: 99%

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GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis

Fuentelsaz-Romero

Cuervo

Estrada-Capetillo

et al. 2020

Preprint

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Background and Aims: GM-CSF-dependent macrophage polarization hasbeen demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.Methods:Synovial tissue (ST)from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12 and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.Results:Synovial stromal cells (FAP+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypesshowed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA and established RA and PsA patients, respectively.Conclusions: GM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.

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Section: Discussionmentioning

confidence: 99%

“…2A). In fact, the leading edge of the GSEA revealed the genes encoding activin A (INHBA), the metalloproteinase MMP12 and the chemokine CCL17 [31] ( Fig. 2A).…”

Section: Clinical and Demographic Featuresmentioning

confidence: 99%

GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis

Fuentelsaz-Romero

Cuervo

Estrada-Capetillo

et al. 2020

Preprint

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“…6). One the one hand, GM-CSF can promote myelopoiesis by mobilizing progenitor myeloid cells to sites of SARS-CoV-2 infection, and facilitating their proliferation and differentiation into various innate immune cells, such as monocytes, macrophages and dendritic cells 30 . On the other hand, GM-CSF can also polarize mature myeloid cells into a pro-inflammatory phenotype, and stimulate the production of various proinflammatory cytokines (e.g., TNF, IL-1β and IL-6) and chemokines (e.g., MCP-1) 30 .…”

Section: Discussionmentioning

confidence: 99%

Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GM-CSF Induction

Qiang

Zhu

et al. 2020

Preprint

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A severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has recently caused a pandemic COVID-19 disease that infected more than 25.6 million and killed 852,000 people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its envelope spike protein for binding the host angiotensin-converting enzyme 2 (ACE2) to gain viral entry. Currently, extensive efforts are being made to produce vaccines against a surface fragment of a SARS-CoV-2, such as the spike protein, in order to boost protective antibody responses. It was previously unknown how spike protein-targeting antibodies would affect innate inflammatory responses to SARS-CoV-2 infections. Here we generated a highly purified recombinant protein corresponding to the RBM of SARS-CoV-2, and used it to screen for cross-reactive monoclonal antibodies (mAbs). We found two RBM-binding mAbs that competitively inhibited its interaction with human ACE2, and specifically blocked the RBM-induced GM-CSF secretion in both human monocyte and murine macrophage cultures. Our findings have suggested a possible strategy to prevent SARS-CoV-2-elicited cytokine storm, and provided a potentially useful criteria for future assessment of innate immune-modulating properties of various SARS-CoV-2 vaccines.

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“…Recent studies have found higher levels of circulating GM-CSF-expressing leukocytes in patients with COVID-19 [ 70 ]. Based on the animal studies, clinical trials are underway to study if inhibition of GM-CSF could be beneficial to maintain lung homeostasis, reduce the hyperinflammation, and help in the lung pathogen clearance [ 71 , 72 ]. Contrarily, the benefit of administering the GM-CSF to patients with COVID-19 is also an ongoing debate.…”

Section: White Blood Cells Abnormalities and Covid-19mentioning

confidence: 99%

A review on how to do hematology consults during COVID-19 pandemic

Sahu

Černý

2021

Blood Reviews

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The ongoing COVID-19 pandemic is the most trending and talked topic across the World. From its point of origin in Wuhan, China to clinical laboratory at NIH, a mere six-month-old SARS-CoV-2 virus is keeping the clinicians, and scientists busy at various fronts. However, COVID-19 is an emerging and evolving disease and each day brings in more data, new figures, and findings from the field of clinical practice. The role of hematologists has been increasingly recognized during the current pandemic because of several reasons. Most important of them are the characteristic hematological findings of COVID-19 patients that also have prognostic implications and that were not seen in other viral infections. The treatment of hematological complications in COVID-19 patients is very challenging given the critical care setting. There are interim and limited guidelines thus far due to the novelty of the disease. As this remains to be a quite fluid situation, all the appropriate medical societies including the major hematology bodies are proposing initial and interim guidelines (e.g. ASH guideline). This puts a hematologist on consult service in a dubious position where, he/she must tailor the recommendations on case to case basis. The purpose of this review is to provide the background context about the impact of COVID-19 on the blood system and to summarize the current interim guidelines to manage the associated hematological issues in COVID-19 infection.

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GM-CSF in inflammation

Cited by 202 publications

References 221 publications

GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis

GM-CSF Expression and Macrophage Polarization in Joints of Undifferentiated Arthritis Patients Evolving to Rheumatoid Arthritis or Psoriatic Arthritis

Monoclonal Antibodies Capable of Binding SARS-CoV-2 Spike Protein Receptor Binding Motif Specifically Prevent GM-CSF Induction

A review on how to do hematology consults during COVID-19 pandemic

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