Macrophages clean up: efferocytosis and microbial control

Martin, Constance; Peters, Kristen N.; Behar, Samuel M.

doi:10.1016/j.mib.2013.10.007

Cited by 152 publications

(137 citation statements)

References 52 publications

(51 reference statements)

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…The engulfment of apoptotic cells relies on the signaling of Rho family GTPases, specifically Rac1, and subsequent cytoskeletal reorganization 31, 32, 33. Consistent with the increase in the number of apoptotic cells engulfed by macrophages (Fig.…”

Section: Resultssupporting

confidence: 66%

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Atomura

Sanui

Fukuda

et al. 2016

Immunity, Inflammation and Disease

View full text Add to dashboard Cite

Periodontitis is a chronic inflammatory disorder caused by specific bacteria residing in the biofilm, particularly Porphyromonas gingivalis (Pg). Sprouty2 (Spry2) functions as a negative regulator of the fibroblast growth factor (FGF) signaling pathway. We previously demonstrated that sequestration of Spry2 induced proliferation and osteogenesis in osteoblastic cells by basic FGF (bFGF) and epidermal growth factor (EGF) stimulation in vitro, but diminished cell proliferation in gingival epithelial cells. In addition, Spry2 knockdown in combination with bFGF and EGF stimulation increases periodontal ligament cell proliferation and migration accompanied by prevention of osteoblastic differentiation. In this study, we investigated the mechanisms through which Spry2 depletion by interferon (IFN) γ and Pg lipopolysaccharide (LPS) stimulation affected the physiology of macrophages in vitro. Transfection of macrophages with Spry2 small‐interfering RNA (siRNA) promoted the expression of genes characteristic of M2 alternative activated macrophages, induced interleukin (IL)‐10 expression, and enhanced arginase activity, even in cells stimulated with IFNγ and Pg LPS. In addition, we found that phosphoinositide 3‐kinase (PI3K) and AKT activation by Spry2 downregulation enhanced efferocytosis of apoptotic cells by increasing Rac1 activation and decreasing nuclear factor kappa B (NFκB) p65 phosphorylation but not signal transducer and activator of transcription 1 (STAT1) phosphorylation. Collectively, our results suggested that topical administration of Spry2 inhibitors may efficiently resolve inflammation in periodontal disease as macrophage‐based anti‐inflammatory immunotherapy and may create a suitable environment for periodontal wound healing. These in vitro findings provide a molecular basis for new therapeutic approaches in periodontal tissue regeneration.

show abstract

Section: Resultssupporting

confidence: 66%

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Atomura

Sanui

Fukuda

et al. 2016

Immunity, Inflammation and Disease

View full text Add to dashboard Cite

show abstract

“…The main role of macrophages it to clear apoptotic 'corpses' by using efferocytosis, a process that is related to both macropinocytosis and phagocytosis. This clearance mechanism limits inflammation and can also result in the destruction of pathogens that trigger apoptosis (Martin et al, 2014). Efferocytosis relies on the presence on the surface of dead and dying cells of molecules (often referred to as 'eat-me' signals) that are not present on healthy cells, notably phosphatidylserine.…”

Section: Macropinocytosis In Immunity and Infectionmentioning

confidence: 99%

Uses and abuses of macropinocytosis

Bloomfield

Kay

2016

Journal of Cell Science

168

171

View full text Add to dashboard Cite

Macropinocytosis is a means by which eukaryotic cells ingest extracellular liquid and dissolved molecules. It is widely conserved amongst cells that can take on amoeboid form and, therefore, appears to be an ancient feature that can be traced back to an early stage of evolution. Recent advances have highlighted how this endocytic process can be subverted during pathology -certain cancer cells use macropinocytosis to feed on extracellular protein, and many viruses and bacteria use it to enter host cells. Prion and prion-like proteins can also spread and propagate from cell to cell through macropinocytosis. Progress is being made towards using macropinocytosis therapeutically, either to deliver drugs to or cause cell death by inducing catastrophically rapid fluid uptake. Mechanistically, the Ras signalling pathway plays a prominent and conserved activating role in amoebae and in mammals; mutant amoebae with abnormally high Ras activity resemble tumour cells in their increased capacity for growth using nutrients ingested through macropinocytosis. This Commentary takes a functional and evolutionary perspective to highlight progress in understanding and use of macropinocytosis, which is an ancient feeding process used by single-celled phagotrophs that has now been put to varied uses by metazoan cells and is abused in disease states, including infection and cancer.

show abstract

“…2H). This secondary uptake most likely includes phagocytosis of the dying or dead cells, which is called efferocytosis (Martin et al, 2013). The secondary uptake of bacterial content that had initially been sequestered by macrophages or neutrophils was performed by macrophages in ∼85% of the cases (Fig.…”

Section: Efferocytosis Of Dead Cells By Macrophagesmentioning

confidence: 99%

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Hosseini

Lamers

Soltani

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Macrophages and neutrophils are the first responders to invading pathogens and contribute strongly to the host defense against intracellular pathogens. The collective interplay and dynamic interactions between these leukocytes are to a large extent not understood. In the present study, we have investigated their role using a combination of confocal laser-scanning and electron microscopy in a zebrafish model for tuberculosis, a local Mycobacterium marinum infection in the tissue of the larval tail fin. Our results show that neutrophils are efficient in phagocytosis of mycobacteria and that they contribute largely to their dissemination. Macrophages appear to play a major role in efferocytosis, phagocytosis of dead cells that contain bacterial content. Phagocytic cells with large bacterial aggregates are formed that can be extruded out of the tissue after cell death. Alternatively, these excessively infected cells can undergo necrosis leading to immediate recruitment of surrounding leukocytes and subsequent phagocytosis of released bacteria. Our data show that these necrotic burst events result in progression of the infection, whereas extrusion abates the infection.

show abstract

Macrophages clean up: efferocytosis and microbial control

Cited by 152 publications

References 52 publications

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Inhibition of Sprouty2 polarizes macrophages toward an M2 phenotype by stimulation with interferon γ andPorphyromonas gingivalislipopolysaccharide

Uses and abuses of macropinocytosis

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Contact Info

Product

Resources

About