Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation

Dudeck, Jan; Kotrba, Johanna; Immler, Roland; Hoffmann, Aaron; Voß, Martin; Alexaki, Vasileia Ismini; Morton, Lorena; Jahn, Stephan R.; Katsoulis‐Dimitriou, Konstantinos; Winzer, Simon; Kollias, G.; Fischer, Thomas; Nedospasov, Sergei A.; Dunay, Ildikò Rita; Chavakis, Triantafyllos; Müller, Andreas J.; Schraven, Burkhart; Sperandio, Markus; Dudeck, Anne

doi:10.1016/j.immuni.2020.12.017

Cited by 63 publications

(58 citation statements)

References 64 publications

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“…In contrast, we determined that perivascular MCs have the capacity to pass the vessel wall and directionally degranulate into the vessel lumen. After being infused into the bloodstream, MC-TNF directly primes circulating Nph via TNFR1 on the Nph surface and thereby allows their efficient extravasation to the inflamed skin [ 15 ]. Importantly, MC-mediated early recruitment of Nph is not only the driving force behind the amplitude of skin inflammation upon elicitation but is also required for efficient sensitization.…”

Section: Mast Cell Contribution To Inflammatory Skin Disordersmentioning

confidence: 99%

“…Under physiologic conditions, MCs are located in the dermis, near blood vessels, nerves and hair follicles [ 6 , 13 ]. Perivascular MCs display an elongated cell shape compared to interstitial MCs and, in the case of arterioles, even line the vessel in parallel to the vessel axis [ 14 , 15 ]. Additionally, we recently demonstrated that a distinct number of perivascular MCs were not only attached to the vessel exterior.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, we recently demonstrated that a distinct number of perivascular MCs were not only attached to the vessel exterior. They formed intraluminal sheets, even under physiologic conditions, and constituted a part of the vascular unit directly in alignment with endothelial cells (ECs) [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Voß

Kotrba

Gaffal

et al. 2021

IJMS

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Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

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Section: Mast Cell Contribution To Inflammatory Skin Disordersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Voß

Kotrba

Gaffal

et al. 2021

IJMS

Self Cite

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“…In some situations, TNF from mast cells can be directly cytotoxic [ 56 ]. TNF has also been implicated in governing neutrophil infiltration of inflamed skin [ 57 ], mast cell-mediated dendritic cell (DC) mobilization [ 58 , 59 , 60 ], as well as the local recruitment of effector cells into mast cell rich sites [ 61 ]. TNF can also enhance mast cell-mediated proliferation of CD3 + T cells in culture [ 62 ].…”

Section: Mast Cell Key Mediators That Influence Cutaneous and Mammary Tumorsmentioning

confidence: 99%

Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role

Hanes

Giacomantonio

Marshall

2021

Cells

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Mast cells are important sentinel cells in host defense against infection and major effector cells in allergic disease. The role of these cells in cancer settings has been widely debated. The diverse range of mast cell functions in both immunity and tissue remodeling events, such as angiogenesis, provides multiple opportunities for mast cells to modify the tumor microenvironment. In this review, we consider both skin and breast cancer settings to address the controversy surrounding the importance of mast cells in the host response to tumors. We specifically address the key mediators produced by mast cells which impact tumor development. The role of environmental challenges in modifying mast cell responses and opportunities to modify mast cell responses to enhance anti-tumor immunity are also considered. While the mast cell’s role in many cancer contexts is complicated and poorly understood, the activities of these tissue resident and radioresistant cells can provide important opportunities to enhance anti-cancer responses and limit cancer development.

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Section: Introductionmentioning

confidence: 99%

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Voß

Kotrba

Gaffal

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Mast cells (MCs) are best known as key effector cells of immediate type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at host-environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first line defense against pathogens. Their main characteristic, the huge amount of preformed pro-inflammatory mediators embedded in secretory granules, allow for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases, but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs all the way from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.

show abstract

Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation

Cited by 63 publications

References 64 publications

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

Mast Cells and Skin and Breast Cancers: A Complicated and Microenvironment-Dependent Role

Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation?

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