{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:32:21Z","timestamp":1781109141365,"version":"3.54.1"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,1,29]]},"abstract":"<jats:p>\n                    We previously reported that mast cells express renin, the rate-limiting enzyme in the renin\u2013angiotensin cascade. We have now assessed whether mast cell renin release triggers angiotensin formation in the airway. In isolated rat bronchial rings, mast cell degranulation released enzyme with angiotensin I-forming activity blocked by the selective renin inhibitor BILA2157. Local generation of angiotensin (ANG II) from mast cell renin elicited bronchial smooth muscle contraction mediated by ANG II type 1 receptors (AT\n                    <jats:sub>1<\/jats:sub>\n                    R). In a guinea pig model of immediate type hypersensitivity, anaphylactic mast cell degranulation in bronchial rings resulted in ANG II-mediated constriction. As in rat bronchial rings, bronchoconstriction (BC) was inhibited by a renin inhibitor, an AT\n                    <jats:sub>1<\/jats:sub>\n                    R blocker, and a mast cell stabilizer. Anaphylactic release of renin, histamine, and \u03b2-hexosaminidase from mast cells was confirmed in the effluent from isolated, perfused guinea pig lung. To relate the significance of this finding to humans, mast cells were isolated from macroscopically normal human lung waste tissue specimens. Sequence analysis of human lung mast cell RNA showed 100% homology between human lung mast cell renin and kidney renin between exons 1 and 10. Furthermore, the renin protein expressed in lung mast cells was enzymatically active. Our results demonstrate the existence of an airway renin\u2013angiotensin system triggered by release of mast-cell renin. The data show that locally produced ANG II is a critical factor governing BC, opening the possibility for novel therapeutic targets in the management of airway disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0709739105","type":"journal-article","created":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T20:46:27Z","timestamp":1200602787000},"page":"1315-1320","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":63,"title":["Mast cell renin and a local renin\u2013angiotensin system in the airway: Role in bronchoconstriction"],"prefix":"10.1073","volume":"105","author":[{"given":"Arul","family":"Veerappan","sequence":"first","affiliation":[{"name":"Departments of *Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia C.","family":"Reid","sequence":"additional","affiliation":[{"name":"Departments of *Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Racha","family":"Estephan","sequence":"additional","affiliation":[{"name":"Departments of *Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Departments of *Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Thadani-Mulero","sequence":"additional","affiliation":[{"name":"Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariselis","family":"Salazar-Rodriguez","sequence":"additional","affiliation":[{"name":"Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Levi","sequence":"additional","affiliation":[{"name":"Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi B.","family":"Silver","sequence":"additional","affiliation":[{"name":"Departments of *Physiology and Biophysics and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,1,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"135","volume-title":"Renal Function","author":"Valtin H","year":"1995","unstructured":"H Valtin, JA Schafer Renal Function (Little, Brown, Boston), pp. 135\u2013138 (1995)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(93)90403-U"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00313.2002"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.22.4.513"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199508000-00009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112566"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-124-1-218"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1969.tb07982.x"},{"key":"e_1_3_3_9_2","first-page":"F989","volume":"264","author":"Paxton WG","year":"1993","unstructured":"WG Paxton, M Runge, C Horaist, C Cohen, RW Alexander, KE Bernstein Am J Physiol 264, F989\u2013F995 (1993).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004180000235"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403208101"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25713"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-3278(03)00081-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.49.5.492"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(98)00265-X"},{"key":"e_1_3_3_16_2","first-page":"211","volume":"255","author":"Wong PC","year":"1990","unstructured":"PC Wong, WA Price, AT Chiu, JV Duncia, DJ Carini, RR Wexler, AL Johnson, PB Timmermans J Pharmacol Exp Ther 255, 211\u2013217 (1990).","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_3_17_2","first-page":"79","volume":"121","author":"Hargreave FE","year":"1982","unstructured":"FE Hargreave, G Ryan, NC Thomson, PM O'Byrne, K Latimer, EF Juniper Eur J Respir Dis Suppl 121, 79\u201388 (1982).","journal-title":"Eur J Respir Dis Suppl"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.07.007"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01966600"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1980.tb10854.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/33.1.2578142"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2410583"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.5.1121"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(75)90117-X"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1159\/000137308"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.36.4.520"},{"key":"e_1_3_3_27_2","first-page":"269","volume":"13","author":"Lewis A","year":"1983","unstructured":"A Lewis, A Blumenthal, A Dervinis Inflamm Res 13, 269\u2013275 (1983).","journal-title":"Inflamm Res"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200004150-00046"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2744(78)90089-X"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)90473-E"},{"key":"e_1_3_3_31_2","first-page":"140","volume":"77","author":"Unger T","year":"1988","unstructured":"T Unger, E Badoer, D Ganten, RE Lang, R Rettig Circulation 77, 140\u2013154 (1988).","journal-title":"Circulation"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.80.2.159"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.3.697"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012705"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.95.08111838"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0954-6111(97)90007-X"},{"key":"e_1_3_3_37_2","first-page":"209","volume":"43","author":"Galli SJ","year":"1993","unstructured":"SJ Galli, JR Gordon, BK Wershil Agents Actions Suppl 43, 209\u2013220 (1993).","journal-title":"Agents Actions Suppl"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199301283280408"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-001-0082-y"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00482-9"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(69)90490-1"},{"key":"e_1_3_3_42_2","first-page":"93","volume-title":"Human Inflammatory Disease, Clinical Immunology","author":"Levi R","year":"1988","unstructured":"R Levi Human Inflammatory Disease, Clinical Immunology, eds G Marone, LM Lichtenstein, M Condorelli, AS Fauci (B. C. Decker, Toronto), pp. 93\u2013105 (1988)."},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.4049\/jimmunol.123.4.1445","volume":"123","author":"Schwartz LB","year":"1979","unstructured":"LB Schwartz, KF Austen, SI Wasserman J Immunol 123, 1445\u20131450 (1979).","journal-title":"J Immunol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0709739105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T18:19:05Z","timestamp":1684174745000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0709739105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,29]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2008,1,29]]}},"alternative-id":["10.1073\/pnas.0709739105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0709739105","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1103024.558995","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,29]]},"assertion":[{"value":"2007-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}