{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T08:29:07Z","timestamp":1759048147989},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,12,24]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>The alarming increase in the incidence of allergic diseases in the past decade has led to a clear call for more effective treatment. Recently, we reported on the construction of a chimeric protein for targeted elimination of cells expressing Fc\u03b5RI receptors. This chimeric protein, designated Fc2\u2032-3-PE40, is composed of a Fc fragment of mouse IgE attached to a truncated form of Pseudomonas exotoxin. The Fc2\u2032-3-PE40 chimeric protein was found to be highly cytotoxic to mouse mast cell lines and primary mouse mast cells. We now demonstrate that Fc2\u2032-3-PE40 successfully prevents the development of passive cutaneous anaphylaxis reaction (PCA) in mice. Treatment with Fc2\u2032-3-PE40 for 7\u2003days prevented the PCA reaction in mice by 80% compared with that in control mice given only PBS. Fc2\u2032-3-PE40M, the mutated, enzymatically inactive analogue of Fc2\u2032-3-PE40, did not display this activity. Fc2\u2032-3-PE40 was also effective when given as a single dose 16\u2003h before antigen exposure, resulting in complete inhibition of the PCA reaction. Moreover, treatment with Fc2\u2032-3-PE40 did not cause mast cell degranulation, as the serum histamine values of mice treated with Fc2\u2032-3-PE40 were within the range obtained for control, untreated mice. Thus, the Fc2\u2032-3-PE40 chimeric protein offers a novel approach to the treatment of allergic disorders.<\/jats:p>","DOI":"10.1046\/j.1365-2249.2000.01151.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:19:47Z","timestamp":1047377987000},"page":"398-403","source":"Crossref","is-referenced-by-count":10,"title":["Targeted Fc2\u2032-3-PE40 chimeric protein abolishes passive cutaneous anaphylaxis in mice"],"prefix":"10.1093","volume":"119","author":[{"given":"A","family":"Fishman","sequence":"first","affiliation":[{"name":"Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Prus","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hadassah University Hospital, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Belostotsky","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Lorberboum-Galski","sequence":"additional","affiliation":[{"name":"Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"2022011221072326300_b1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1600-065X.1978.tb01462.x","article-title":"Mechanism of reaginic hypersensitivity and IgE antibody response","volume":"41","author":"Ishizaka","year":"1978","journal-title":"Immunol Rev"},{"key":"2022011221072326300_b2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1128\/mr.48.3.199-221.1984","article-title":"Bacterial toxins: cellular mechanisms of action","volume":"48","author":"Middlebrook","year":"1984","journal-title":"Microbiol Rev"},{"key":"2022011221072326300_b3","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1073\/pnas.86.11.4215","article-title":"Cytotoxic activity of a recombinant fusion protein between interleukin 4 and Pseudomonas exotoxin","volume":"86","author":"Ogata","year":"1989","journal-title":"Proc Natl Acad Sci USA"},{"key":"2022011221072326300_b4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/335369a0","article-title":"Selective killing of HIV-infected cells by recombinant human CD4\u2013Pseudomonas exotoxin hybrid protein","volume":"335","author":"Chaudhary","year":"1988","journal-title":"Nature (London)"},{"key":"2022011221072326300_b5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3109\/15569549409006483","article-title":"Interleukin 2\u2013Pseudomonas exotoxin A (IL2\u2013PE40) chimeric protein for targeted immunotherapy and the study of immune response","volume":"13","author":"Lorberboum-Galski","year":"1994","journal-title":"J Toxicol-Toxin Rev"},{"key":"2022011221072326300_b6","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/eji.1830270220","article-title":"Targeted elimination of cells expressing the high affinity receptor for IgE, (FceRI) by a Pseudomonas exotoxin-based chimeric protein","volume":"27","author":"Fishman","year":"1997","journal-title":"Eur J Immunol"},{"key":"2022011221072326300_b7","doi-asserted-by":"crossref","first-page":"16934","DOI":"10.1021\/bi980995m","article-title":"Role of caspases in immunotoxin-induced apoptosis of cancer cells","volume":"37","author":"Keppler-Hafkemeyer","year":"1998","journal-title":"Biochemistry"},{"key":"2022011221072326300_b8","first-page":"347","article-title":"Induction of apoptosis in multidrug-resistant and radiation-resistant acute myeloid leukemia cells by recombinant fusion toxin directed against the human granulocyte macrophage colony-stimulating factor receptor","volume":"3","author":"Perentesis","year":"1997","journal-title":"Clin Cancer Res"},{"key":"2022011221072326300_b9","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/(SICI)1097-0215(19961104)68:3<349::AID-IJC13>3.0.CO;2-3","article-title":"Induction of apoptosis by ribosome-inactivating proteins and related immunotoxins","volume":"68","author":"Bolognesi","year":"1996","journal-title":"Int J Cancer"},{"key":"2022011221072326300_b10","volume-title":"Pocket guide for asthma management and prevention. 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