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• W2899207819 abstract "In their recent interesting review, Olivera et al1Olivera A. Beaven M.A. Metcalfe D.D. Mast cells signal their importance in health and disease.J Allergy Clin Immunol. 2018; 142: 381-393Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar stress the importance of mast cells as targets not only of allergic stimuli but also of many environmental and cationic molecules. The authors then focus on the role of the cytokine IL-33 in allergen-induced mast cell responses. We believe it is appropriate to also discuss the effect of IL-33 on mast cell mediators synthesized de novo, in addition to augmentation of allergic stimulation and secretion of granule-stored mediators, such as tryptase. Recently, we reported that IL-33 augments allergen-induced secretion of IL-31, which is important in pruritus, as well as stimulates secretion of IL-31 from human mast cells in the absence of an allergic stimulus.2Petra A.I. Tsilioni I. Taracanova A. Katsarou-Katsari A. Theoharides T.C. Interleukin 33 and interleukin 4 regulate interleukin 31 gene expression and secretion from human laboratory of allergic diseases 2 mast cells stimulated by substance P and/or immunoglobulin E.Allergy Asthma Proc. 2018; 39: 153-160Crossref PubMed Scopus (34) Google Scholar It is also pertinent to discuss the effect of IL-33 on nonallergic stimuli. We also showed that IL-33 augments the effect of the proinflammatory peptide substance P (SP) in stimulating secretion of impressive amounts of vascular endothelial growth factor (VEGF)3Theoharides T.C. Zhang B. Kempuraj D. Tagen M. Vasiadi M. Angelidou A. et al.IL-33 augments substance P-induced VEGF secretion from human mast cells and is increased in psoriatic skin.Proc Natl Acad Sci U S A. 2010; 107: 4448-4453Crossref PubMed Scopus (274) Google Scholar and TNF,4Taracanova A. Tsilioni I. Conti P. Norwitz E.R. Leeman S.E. Theoharides T.C. Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin.Proc Natl Acad Sci U S A. 2018; 115: E9381-E9390Crossref PubMed Scopus (65) Google Scholar without concomitant secretion of tryptase, from human mast cells. The 1000-fold increase in secretion of TNF stimulated by IL-33 administered together with SP involves some interaction between their respective receptors. This conclusion is based on the fact that the receptor for IL-33, ST2, was coprecipitated with the receptor for SP, neurokinin-1 (NK-1).4Taracanova A. Tsilioni I. Conti P. Norwitz E.R. Leeman S.E. Theoharides T.C. Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin.Proc Natl Acad Sci U S A. 2018; 115: E9381-E9390Crossref PubMed Scopus (65) Google Scholar Moreover, preincubation of human mast cells with NK1 antagonists also inhibited the effect of IL-33 used by itself without SP.4Taracanova A. Tsilioni I. Conti P. Norwitz E.R. Leeman S.E. Theoharides T.C. Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin.Proc Natl Acad Sci U S A. 2018; 115: E9381-E9390Crossref PubMed Scopus (65) Google Scholar ST2 properly known as interleukin 1 receptor-like 1 is a member of the IL-1 receptor family. We had reported that IL-1 stimulates human mast cells to secrete IL-6 without tryptase.5Kandere-Grzybowska K. Letourneau R. Kempuraj D. Donelan J. Poplawski S. Boucher W. et al.IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells.J Immunol. 2003; 171: 4830-4836Crossref PubMed Scopus (194) Google Scholar This finding is important given that serum levels of IL-6 are elevated and correlate with disease severity in patients with systemic mastocytosis.6Theoharides T.C. Boucher W. Spear K. Serum interleukin-6 reflects disease severity and osteoporosis in mastocytosis patients.Int Arch Allergy Immunol. 2002; 128: 344-350Crossref PubMed Scopus (87) Google Scholar, 7Brockow K. Akin C. Huber M. Metcalfe D.D. IL-6 levels predict disease variant and extent of organ involvement in patients with mastocytosis.Clin Immunol. 2005; 115: 216-223Crossref PubMed Scopus (71) Google Scholar That mast cells can secrete mediators without tryptase (Table I) and that IL-33 augments nonallergic stimuli such as SP is critical for understanding the role of mast cells in diseases such as mastocytosis and mast cell activation syndrome in which most symptoms are neither due to allergic triggers nor due to tryptase.Table IExamples of mediators secreted without tryptase from human mast cellsNonallergic stimuliDe novo synthesized mediatorsGrowth factors CRHVEGF SCFIL-6Cytokines IL-1IL-6 IL-33IL-31 IL-33 + SPVEGF, TNFPathogens Borrelia b. (Lyme disease)TNF Sporothrix (mold)IL-6, TNFCRH, Corticotropin-releasing hormone; SCF, stem cell factor. Open table in a new tab CRH, Corticotropin-releasing hormone; SCF, stem cell factor. Mast cells signal their importance in health and diseaseJournal of Allergy and Clinical ImmunologyVol. 142Issue 2PreviewFcεRI is the primary receptor in mast cells that mediates allergic reactions by inducing rapid release of mediators, an adaptive immune response that might have evolved as a host defense against parasites and venoms. Yet it is apparent that mast cells are also activated through non-IgE receptors, the significance of which is just beginning to be understood. This includes the Mas-related G protein–coupled receptor X2, which might contribute to reactions to diverse antimicrobials and polybasic compounds, and the adhesion G protein–coupled receptor E2, variants of which are associated with familial vibratory urticaria and are activated by mechanical vibration. Full-Text PDF ReplyJournal of Allergy and Clinical ImmunologyVol. 143Issue 1PreviewWe thank Theoharides and Leeman1 for their positive comments on our review,2 which focused on recent developments in the understanding of human mast cell biology. It is gratifying to see this large number of recent scientific reports from which we selected only a portion of many interesting and novel experimental approaches and observations. The understanding of mast cell biology has lagged somewhat behind studies on other effector cells because mast cells do not normally occur in blood, there is no human condition characterized by the absence of mast cells in all tissues, and there is no pharmacologic therapy that specifically and only silences mast cell function. Full-Text PDF" @default.
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• W2899207819 title "Effect of IL-33 on de novo synthesized mediators from human mast cells" @default.
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