Distribution of mast cells within the mouse heart and its dependency on Mitf

Ingason, Arnar B.; Mechmet, Fatich; Atacho, Diahann A. M.; Steingrı́msson, Eirı́kur; Petersen, Petur H.

doi:10.1016/j.molimm.2018.11.009

Cited by 25 publications

(21 citation statements)

References 39 publications

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“…Mast cells are present in strategically important locations of murine [43,92] and human heart [48,49,51,77]. Mast cells are present in atherosclerotic lesions [50,93] and promote atherogenesis [89].…”

Section: Discussionmentioning

confidence: 99%

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Superantigenic Activation of Human Cardiac Mast Cells

Varricchi

Loffredo

Borriello

et al. 2019

IJMS

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B cell superantigens, also called immunoglobulin superantigens, bind to the variable regions of either the heavy or light chain of immunoglobulins mirroring the lymphocyte-activating properties of classical T cell superantigens. Protein A of Staphylococcus aureus, protein L of Peptostreptococcus magnus, and gp120 of HIV are typical immunoglobulin superantigens. Mast cells are immune cells expressing the high-affinity receptor for IgE (FcεRI) and are strategically located in the human heart, where they play a role in several cardiometabolic diseases. Here, we investigated whether immunoglobulin superantigens induced the activation of human heart mast cells (HHMCs). Protein A induced the de novo synthesis of cysteinyl leukotriene C4 (LTC4) from HHMCs through the interaction with IgE VH3+ bound to FcεRI. Protein L stimulated the production of prostaglandin D2 (PGD2) from HHMCs through the interaction with κ light chains of IgE. HIV glycoprotein gp120 induced the release of preformed (histamine) and de novo synthesized mediators, such as cysteinyl leukotriene C4 (LTC4), angiogenic (VEGF-A), and lymphangiogenic (VEGF-C) factors by interacting with the VH3 region of IgE. Collectively, our data indicate that bacterial and viral immunoglobulin superantigens can interact with different regions of IgE bound to FcεRI to induce the release of proinflammatory, angiogenic, and lymphangiogenic factors from human cardiac mast cells.

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Section: Discussionmentioning

confidence: 99%

“…Mast cells are tissue resident immune cells present in most connective tissues including murine [43,44,45], canine [46,47], and human heart [48,49,50,51]. Mast cells are canonically considered key effectors of allergic responses [52,53,54,55,56] and are critical sentinels in immunity [57,58].…”

Section: Introductionmentioning

confidence: 99%

Superantigenic Activation of Human Cardiac Mast Cells

Varricchi

Loffredo

Borriello

et al. 2019

IJMS

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“…Data shows that MC density increases in murine hearts after damage (22, 28, 30, 33, 76, 108, 109), but it is unclear if statistically significant increases in MC content have physiological relevance, or that murine cardiac MC responses mirror those in humans. Recent evidence suggests that the distribution of mast cells in the hearts of mice also differs considerably from that in humans (110).…”

Section: Confounding Factors In Mast Cell Cardiac Fibrosis Researchmentioning

confidence: 99%

Mast Cells in Cardiac Fibrosis: New Insights Suggest Opportunities for Intervention

et al. 2019

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Mast cells (MC) are innate immune cells present in virtually all body tissues with key roles in allergic disease and host defense. MCs recognize damage-associated molecular patterns (DAMPs) through expression of multiple receptors including Toll-like receptors and the IL-33 receptor ST2. MCs can be activated to degranulate and release pre-formed mediators, to synthesize and secrete cytokines and chemokines without degranulation, and/or to produce lipid mediators. MC numbers are generally increased at sites of fibrosis. They are potent, resident, effector cells producing mediators that regulate the fibrotic process. The nature of the secretory products produced by MCs depend on micro-environmental signals and can be both pro- and anti-fibrotic. MCs have been repeatedly implicated in the pathogenesis of cardiac fibrosis and in angiogenic responses in hypoxic tissues, but these findings are controversial. Several rodent studies have indicated a protective role for MCs. MC-deficient mice have been reported to have poorer outcomes after coronary artery ligation and increased cardiac function upon MC reconstitution. In contrast, MCs have also been implicated as key drivers of fibrosis. MC stabilization during a hypertensive rat model and an atrial fibrillation mouse model rescued associated fibrosis. Discrepancies in the literature could be related to problems with mouse models of MC deficiency. To further complicate the issue, mice generally have a much lower density of MCs in their cardiac tissue than humans, and as such comparing MC deficient and MC containing mouse models is not necessarily reflective of the role of MCs in human disease. In this review, we will evaluate the literature regarding the role of MCs in cardiac fibrosis with an emphasis on what is known about MC biology, in this context. MCs have been well-studied in allergic disease and multiple pharmacological tools are available to regulate their function. We will identify potential opportunities to manipulate human MC function and the impact of their mediators with a view to preventing or reducing harmful fibrosis. Important therapeutic opportunities could arise from increased understanding of the impact of such potent, resident immune cells, with the ability to profoundly alter long term fibrotic processes.

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“…In the heart, histamine originates from sympathetic nerves [8] and mast cells that are found at varying species-dependent densities [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. Cardiac mast cells are of the connective tissue phenotype and are found mainly in the epicardium (50%) and myocardium (45%), with only a few cells found in the endocardium (5%) [25]. Within these regions, mast cells are localized to both interstitial and perivascular regions [15,[25][26][27][28], with many cardiac mast cells making close connections to neurons [29].…”

Section: Introductionmentioning

confidence: 99%

Histamine receptors in heart failure

Levick

2021

Heart Fail Rev

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The biogenic amine, histamine, is found predominantly in mast cells, as well as specific histaminergic neurons. Histamine exerts its many and varied actions via four G-protein-coupled receptors numbered one through four. Histamine has multiple effects on cardiac physiology, mainly via the histamine 1 and 2 receptors, which on a simplified level have opposing effects on heart rate, force of contraction, and coronary vasculature function. In heart failure, the actions of the histamine receptors are complex, the histamine 1 receptor appears to have detrimental actions predominantly in the coronary vasculature, while the histamine 2 receptor mediates adverse effects on cardiac remodeling via actions on cardiomyocytes, fibroblasts, and even endothelial cells. Conversely, there is growing evidence that the histamine 3 receptor exerts protective actions when activated. Little is known about the histamine 4 receptor in heart failure. Targeting histamine receptors as a therapeutic approach for heart failure is an important area of investigation given the over-the-counter access to many compounds targeting these receptors, and thus the relatively straight forward possibility of drug repurposing. In this review, we briefly describe histamine receptor signaling and the actions of each histamine receptor in normal cardiac physiology, before describing in more detail the known role of each histamine receptor in adverse cardiac remodeling and heart failure. This includes information from both clinical studies and experimental animal models. It is the goal of this review article to bring more focus to the possibility of targeting histamine receptors as therapy for heart failure.

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Distribution of mast cells within the mouse heart and its dependency on Mitf

Cited by 25 publications

References 39 publications

Superantigenic Activation of Human Cardiac Mast Cells

Superantigenic Activation of Human Cardiac Mast Cells

Mast Cells in Cardiac Fibrosis: New Insights Suggest Opportunities for Intervention

Histamine receptors in heart failure

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