Activation of human mast cells through the platelet-activating factor receptor

Kajiwara, Naoki; Sasaki, Tomomi; Bradding, Peter; Cruse, Glenn; Sagara, Hironori; Ohmori, Kazuo; Saito, Hirohisa; Ra, Chisei; Okayama, Yoshimichi

doi:10.1016/j.jaci.2010.01.056

Cited by 134 publications

(128 citation statements)

References 45 publications

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“…In humans, four MrgX genes, MrgX1-X4 are known (24,26). Although originally thought to be specifically expressed in dorsal root ganglia, it now appears that human skin mast cells, cord blood-derived mast cells, CD34 ϩ cell-derived mast cells, and a human mast cell line, LAD2, express MrgX2 (27,28,49). Most interestingly, this receptor is not present in human lymph nodes, spleen, or peripheral blood leukocytes (28).…”

Section: Discussionmentioning

confidence: 99%

Mas-related Gene X2 (MrgX2) Is a Novel G Protein-coupled Receptor for the Antimicrobial Peptide LL-37 in Human Mast Cells

Subramanian

Gupta

Guo

et al. 2011

Journal of Biological Chemistry

190

241

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Background: Antimicrobial peptide LL-37 activates leukocytes, mast cells, and endothelial cells. Results: LL-37 causes chemotaxis, degranulation, and chemokine production in human mast cells expressing MrgX2, but it does not induce receptor desensitization. Conclusion: MrgX2 is a novel receptor for LL-37 in human mast cells, and this receptor is resistant to regulation. Significance: This study has important implications for innate immunity and inflammation.

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Section: Discussionmentioning

confidence: 99%

Mas-related Gene X2 (MrgX2) Is a Novel G Protein-coupled Receptor for the Antimicrobial Peptide LL-37 in Human Mast Cells

Subramanian

Gupta

Guo

et al. 2011

Journal of Biological Chemistry

190

241

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“…In the case of mast cells located in the skin, exposure to PAF leads to degranulation of their granules via neuropeptides. 12 Kajiwara et al 13 has demonstrated in vitro that PAF can directly activate mast cells derived from lung tissue through surface PAFRs. An interesting aspect of mast cells that have been highlighted by these studies is that the release of histamine from lung mast cells mastocytes is dependent on the concentration of PAF.…”

Section: Paf and Mast Cellsmentioning

confidence: 99%

Platelet activating factor in allergies

Pałgan

Bartuzi

2015

Int J Immunopathol Pharmacol

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The platelet-activating factor (PAF) produced and released by mast cells, basophils, neutrophils, eosinophils, fibroblasts, platelets, endothelial cells, and even cardiac muscle cells plays an important role in inflammatory and thrombotic diseases. PAF has been shown to be an important mediator in anaphylaxis. Serum level of the factor correlates with the severity of systemic reactions. PAF is also involved in asthamatic patients' bronchoconstriction, mucus hypersecretion, and inflammation of bronchi. Furthermore, increased plasma levels of PAF have been reported in patients with urticarial. Studies have shown that PAF increases the permeability of skin's capillaries and indices the development of wheals, flare, and inflammatory reactions in the skin.This review focuses on the actions of the PAF on the eosinophiles and mast cells. Following that pathophysiological mechanism of the PAF in anaphylaxis bronchial asthma and urticaria was discussed.

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“…No studies have been performed to date on the human mast cell line LAD2. PAF-induced mast cell degranulation is partially dependent on extracellular calcium, as demonstrated in human peripheral blood-derived mast cells [5] and in the human leukemia mast cell line HMC-1 [13].…”

Section: Introductionmentioning

confidence: 89%

“…There is evidence that PAF can activate human lung mast cells (hLMCs), but not skin mast cells, through PAF receptor and phospholipase C-γ1 and -β2 [5]. These findings provide a plausible mechanism whereby PAF mediates an amplification loop for mast cell activation in the generation of the allergic response.…”

Section: Introductionmentioning

confidence: 95%

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Effects of Rupatadine on Platelet- Activating Factor–Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

Muñoz-Cano¹,

Ainsua-Enrich²,

Torres-Atencio³

et al. 2017

J Investig Allergol Clin Immunol

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Background: Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine. Methods: The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs. Results: CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not. Conclusions: This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

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Activation of human mast cells through the platelet-activating factor receptor

Cited by 134 publications

References 45 publications

Mas-related Gene X2 (MrgX2) Is a Novel G Protein-coupled Receptor for the Antimicrobial Peptide LL-37 in Human Mast Cells

Mas-related Gene X2 (MrgX2) Is a Novel G Protein-coupled Receptor for the Antimicrobial Peptide LL-37 in Human Mast Cells

Platelet activating factor in allergies

Effects of Rupatadine on Platelet- Activating Factor–Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

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