{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:08:50Z","timestamp":1773533330949,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T00:00:00Z","timestamp":1225411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>\n                    Mast cells are key components of the immune system, where they help orchestrate the inflammatory response. Aberrant mast cell activation is linked to a variety of allergic diseases, including asthma, eczema, rhinitis, and nasal polyposis, which in combination affect up to 20% of the population in industrialized countries. On activation, mast cells release a variety of signals that target the bronchi and vasculature and recruit other immune cells to the inflammatory site. Prominent among such signals are the cysteinyl leukotrienes, a family of potent proinflammatory lipid mediators comprising leukotriene C\n                    <jats:sub>4<\/jats:sub>\n                    (LTC\n                    <jats:sub>4<\/jats:sub>\n                    ), LTD\n                    <jats:sub>4<\/jats:sub>\n                    , and LTE\n                    <jats:sub>4<\/jats:sub>\n                    . LTC\n                    <jats:sub>4<\/jats:sub>\n                    , the parent compound, is secreted from mast cells following Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through store\u2010operated calcium release\u2010activated calcium (CRAC) channels. Here, we show that activated mast cells release a paracrine signal that evokes Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in spatially separate resting mast cells. The paracrine signal was identified as a cysteinyl leukotriene because\n                    <jats:italic>1<\/jats:italic>\n                    ) RNAi knockdown or pharmacological block of the 5\u2010lipoxygenase enzyme prevented activated mast cells from stimulating resting cells.\n                    <jats:italic>2<\/jats:italic>\n                    ) Block of cysteinyl leukotriene type I receptors on resting mast cells with the clinically prescribed receptor antagonist montelukast prevented their activation by active mast cells.\n                    <jats:italic>3<\/jats:italic>\n                    ) RNAi knockdown of cysteinyl leukotriene type I receptors on resting cells prevented them from responding to the paracrine signal derived from activated mast cells.\n                    <jats:italic>4<\/jats:italic>\n                    ) Purified LTC\n                    <jats:sub>4<\/jats:sub>\n                    evoked Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signals in mast cells that were identical to those triggered by the paracrine signal. Low levels of stimulus intensity released sufficient levels of leukotriene to activate resting cells. Leukotriene secretion still occurred tens of minutes after stimulation, suggesting a role as a long\u2010lasting trigger in mast cell activation. Stimulation of the cysteinyl leukotriene receptor activated CRAC channels and evoked prominent store\u2010operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry. This resulted in further cysteinyl leukotriene production, triggering a positive feedback cascade. Acutely isolated mast cells from patients with allergic rhinitis exhibited store\u2010operated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx through CRAC channels and responded to cysteinyl leukotrienes. Histological analysis of samples taken from patients revealed clustering of mast cells, often located within 20 \u03bcm of each other, a distance sufficient for paracrine signaling by leukotrienes to operate effectively. We conclude that a positivefeedback cascade involving CRAC channels and cysteinyl leukotrienes constitute a novel mechanism for sustaining mast cell activation.\u2014 Di Capite, J., Shirley, A., Nelson, C., Bates, G., Parekh, A. B. Intercellular Ca2+ wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    23, 894\u2013905 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-118935","type":"journal-article","created":{"date-parts":[[2008,10,31]],"date-time":"2008-10-31T20:58:45Z","timestamp":1225486725000},"page":"894-905","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Intercellular Ca\n                    <sup>2+<\/sup>\n                    wave propagation involving positive feedback between CRAC channels and cysteinyl leukotrienes"],"prefix":"10.1096","volume":"23","author":[{"given":"Joseph","family":"Di Capite","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Shirley","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charmaine","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grant","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Ear, Nose and Throat Surgery John Radcliffe Hospital Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anant B.","family":"Parekh","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,10,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(02)00394-1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(99)70370-2"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2003.09.015"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2006.02498.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1992.tb00624.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.294.5548.1871"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6016fje"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2007.00512.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141221498"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-1981(02)00160-9"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/21658"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0407OC"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.1636"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403969200"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5255"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705002200"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/355353a0"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.13.6295"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.4.901"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200502019"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04147"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.05.055"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200604014"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04702"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05122"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1127883"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.08.085"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0603161103"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2003.01786.x"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-004-0029-x"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198406213102502"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/088318704322994958"},{"key":"e_1_2_5_34_1","first-page":"39","article-title":"Mast cell degranulation in nasal polyps","volume":"430","author":"Takasaka T.","year":"1986","journal-title":"Acta Otolaryngol. 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