Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response

Bąbolewska, Edyta; Brzezińska‐Błaszczyk, Ewa

doi:10.1016/j.cellimm.2014.12.006

Cited by 44 publications

(38 citation statements)

References 42 publications

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“…46–51 Unlike the human genome, the rat genome possesses one each of the MrgprA, MrgprC, MrgprD, MrgprE, MrgprF, and MrgprH genes and six MrgprB genes. 20, 19 RT-PCR analysis demonstrated that rat peritoneal MCs (PMCs) express high levels of the MrgprB3 and MrgprB8 and low levels of the MrgprB1, MrgprB2, MrgprB6, and MrgprB9 genes.…”

Section: Mrgprb3 As the Rat Ortholog Of Human Mrgprx2mentioning

confidence: 99%

“…12, 14, 58 HDPs (LL-37 and hBDs) act as potent MC chemoattactants, 46, 59, 60 and also increase the expression of toll-like receptor-4 (TLR-4) on their surface, which may enhance ability of MCs to detect invading pathogens. 14, 61 MC degranulation plays an important role in host defense by causing increased vascular permeability and by initiating the recruitment of neutrophil to the sites of infection.…”

Section: Mrgprx2 As a Novel Gpcr For Hdps And Its Role In Innate Immumentioning

confidence: 99%

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Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Subramanian¹,

Gupta

Ali

2016

Journal of Allergy and Clinical Immunology

331

312

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Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity and wound healing. MCs are, however, best known for their roles in allergic and inflammatory diseases such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis and asthma. In addition to the high affinity IgE receptor (FcεRI), MCs express numerous G protein coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and are the most common targets of drug therapy. Antimicrobial host defense peptides (HDPs), neuropeptides (NPs), major basic protein (MBP), eosinophil peroxidase (EPO) and many FDA approved peptidergic drugs activate human MCs via a novel GPCR known as MAS-related G protein coupled receptor-X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on plasma membrane and intracellular sites and their selective expression in MCs. In this article, we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch and chronic inflammatory diseases such as urticaria and asthma. We propose that HDPs that kill microbes directly and activate MCs via MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, monoclonal antibodies or small molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders.

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Section: Mrgprb3 As the Rat Ortholog Of Human Mrgprx2mentioning

confidence: 99%

Section: Mrgprx2 As a Novel Gpcr For Hdps And Its Role In Innate Immumentioning

confidence: 99%

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Subramanian¹,

Gupta

Ali

2016

Journal of Allergy and Clinical Immunology

331

312

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“…Cathelicidin LL-37 directly kills pathogens directly by disrupting their membranes, and it neutralizes the activity of bacterial endotoxins. In addition, there is increasing evidence that it exerts proinflammatory effects [3,4], as it acts as a chemoattractant for mast cells, neutrophils, monocytes, and T cells; it also activates inflammatory cells and modulates Toll-like receptors (TLRs) responses and proinflammatory cytokine release [1,5,6,7]. In addition, LL-37 stimulates the production of various chemokines and increases the expression of some chemokine receptors [3,4].…”

mentioning

confidence: 99%

Circulating cathelicidin LL-37 in adult patients with pulmonary infectious diseases

Majewski

Żelechowska

Brzezińska‐Błaszczyk

2017

CIM

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Purpose: The antimicrobial peptide cathelicidin LL-37 plays a role in the immune response in the course of lung infections; however, the exact role of LL-37 in defense mechanisms against bacteria within the respiratory tract is has not been precisely described. The aim of our study was to evaluate LL-37 concentrations in the serum of pulmonary tuberculosis (TB) patients, patients with pneumonia caused by Gram-positive and Gram-negative bacteria and to compare them with those of healthy subjects.Methods: Thirty TB patients, 30 patients with pneumonia caused by Gram-positive bacteria, 30 patients with pneumonia caused by Gram-negative bacteria, and 30 healthy control subjects were enrolled in the study. Serum LL-37 concentration was measured using an enzyme-linked immunosorbent assay (ELISA). Results:The mean (± SEM) LL-37 concentration in patients with TB (13.94±5.13 ng/mL) was significantly higher than that in patients with Gram-positive bacteria-induced pneumonia (7.87±4.58 ng/mL, P=0.00077), in patients with Gram-negative bacteria-induced pneumonia (10.27±3.60 ng/mL, P=0.00730), and in control healthy subjects (1.75±0.71 ng/mL, P=0.00004). Conclusion:Our data suggest that cathelicidin LL-37 is an important element of host defense in the course of bacterial diseases within the respiratory tract, particularly when the infection is caused by an intracellular pathogen.

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“…Pleurocidin, a fish cationic antimicrobial peptide, activates mast cells to secrete CCL2 and CCL4 [23]. The human cathelithicin LL-37 activates degranulation and cytokine secretion, but not the synthesis of arachidonic acid metabolites [24]. …”

Section: Mast Cell Priming and Activation By Exogenous Substancesmentioning

confidence: 99%

News in Cellular Allergology: A Review of the Human Mast Cell and Basophil Granulocyte Literature from January 2013 to May 2015

Hoffmann

2015

Int Arch Allergy Immunol

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Mast cell activation releases the mediators associated with type I allergy. As such, the study of mast cell activation is critical for understanding the allergic reaction, and for developing methods to control it. Importantly, another ligand receptor pair (compound 48/80 and MRGPRX2) that activates mast cells in addition to allergen-IgE-FcεRI has been identified. As mast cells mature in tissue from hematopoietic stem cells, their physiology and pathophysiology is difficult to study. Mast cell lines and mast cells cultured from stem cells are often studied instead of tissue mast cells. There has been some progress in the description of the mechanism of the activation of mast cells, substances limiting mast cell activation and in the catalogue of proteases that mast cells express. Basophil granulocytes express FcεRI, bind IgE and respond to allergen crosslinking in a very similar fashion to mast cells. In the recent literature, basophils were mistakenly described as antigen-presenting cells; this has convincingly been disputed in a number of subsequent publications. Their function in physiology and pathophysiology is not known, but they are frequently used to document allergic sensitisation in the basophil activation test. Significant progress has been made in documenting the relevance of basophil activation as a second-line test in allergy diagnosis. Basophil reactivity and sensitivity may reflect symptom severity and allergen threshold, and are used to document and monitor allergy. The physiology and pathophysiology of allergic effector cells remain an important area of research.

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Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response

Cited by 44 publications

References 42 publications

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases

Circulating cathelicidin LL-37 in adult patients with pulmonary infectious diseases

News in Cellular Allergology: A Review of the Human Mast Cell and Basophil Granulocyte Literature from January 2013 to May 2015

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