{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T05:43:31Z","timestamp":1768283011030,"version":"3.49.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2007,8,27]],"date-time":"2007-08-27T00:00:00Z","timestamp":1188172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000019","name":"Crohn\u2019s and Colitis Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In Crohn\u2019s disease and ulcerative colitis patients, the numbers of neutrophils recovered from stool directly correlates with the severity of disease, implying that neutrophils in the lumen contribute to the tissue destruction; therefore, it is important to understand the mechanisms behind transintestinal epithelial migration. Neutrophil transintestinal epithelial migration to fMLP is appreciated to be CD11b\/CD18 integrin (Mac-1)-dependent, while we recently reported that migration to C5a is Mac-1-independent. Here, we investigated whether phospholipase D (PLD), a signaling molecule linked to chemoattractant activation of neutrophils, is necessary for both Mac-1-dependent and Mac-1-independent migration. Both fMLP and C5a increased neutrophil expression of the Mac-1 activation epitope, indicating PLD was activated. This up-regulation was dose-dependently prevented by incubation of neutrophils in 1-butanol, an inhibitor of PLD activity. Despite this effect on Mac-1, 1-butanol did not prevent neutrophil migration across acellular filters. Incubation in 1-butanol did inhibit fMLP but not C5a-mediated migration across intestinal epithelial cell monolayers, showing that transepithelial migration to fMLP but not C5a is dependent on PLD. The addition of phosphatidic acid, a reaction product of PLD, partially restored fMLP-mediated transepithelial migration in the presence of 1-butanol but not the migration of Mac-1-deficient neutrophil-differentiated HL-60 cells. Thus PLD control over expression of the Mac-1 activation epitope is critical for neutrophil migration to fMLP but not C5a. Moreover, as PLD controls other neutrophil functions, such as the oxidative response, degranulation, and protease release, we could exclude these functions as being important in neutrophil transepithelial migration to C5a.<\/jats:p>","DOI":"10.1189\/jlb.0806528","type":"journal-article","created":{"date-parts":[[2007,8,28]],"date-time":"2007-08-28T00:39:58Z","timestamp":1188261598000},"page":"1575-1584","source":"Crossref","is-referenced-by-count":40,"title":["Neutrophil transepithelial migration in response to the chemoattractant fMLP but not C5a is phospholipase D-dependent and related to the use of CD11b\/CD18"],"prefix":"10.1093","volume":"82","author":[{"given":"Svetlana O","family":"Carrigan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University , Halifax, Nova Scotia , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desmond B S","family":"Pink","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, and the Dalhousie Inflammation Group, Dalhousie University , Halifax, Nova Scotia , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew W","family":"Stadnyk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Dalhousie University , Halifax, Nova Scotia , Canada"},{"name":"Department of Pediatrics, and the Dalhousie Inflammation Group, Dalhousie University , Halifax, Nova Scotia , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,8,27]]},"reference":[{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1136\/gut.26.4.378","article-title":"In vivo assessment of granulocyte migration to diseased bowel in Crohn\u2019s disease","volume":"26","author":"Saverymuttu","year":"1985","journal-title":"Gut"},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/00042737-200103000-00004","article-title":"Gut luminal neutrophil migration is influenced by the anatomical site of Crohn\u2019s disease","volume":"13","author":"Arnott","year":"2001","journal-title":"Eur. 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Immunol."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1007\/BF01296664","article-title":"Chemotactic activity in inflammatory bowel disease, role of leukotriene B4","volume":"32","author":"Lobos","year":"1987","journal-title":"Dig. Dis. Sci."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1136\/gut.39.2.248","article-title":"Mucosal factors inducing neutrophil movement in ulcerative colitis: The role of interleukin 8 and leukotriene B4","volume":"39","author":"Cole","year":"1996","journal-title":"Gut"},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/j.1365-2249.2004.02429.x","article-title":"Neutrophils migrate across intestinal epithelium using \u03b22 (CD11b\/CD18)-independent mechanisms","volume":"136","author":"Blake","year":"2004","journal-title":"Clin. Exp. 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Biochem."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.4049\/jimmunol.152.12.5922","article-title":"Signal transduction pathway in human polymorphonuclear leukocytes for chemotaxis induced by a chemotactic factor. Distinct from the pathway for superoxide anion production","volume":"152","author":"Yasui","year":"1994","journal-title":"J. Immunol."},{"key":"2023033006292969300_","first-page":"927","article-title":"Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins","volume":"91","author":"Sugi","year":"1996","journal-title":"Am. J. Gastroenterol."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1136\/gut.26.9.955","article-title":"111Indium autologous granulocytes in the detection of inflammatory bowel disease","volume":"26","author":"Saverymuttu","year":"1985","journal-title":"Gut"},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"19,588","DOI":"10.1074\/jbc.M513025200","article-title":"Annexin I regulates SKCO-15 cell invasion by signaling through formyl peptide receptors","volume":"281","author":"Babbin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJM199005103221903","article-title":"Enhanced local production of complement components in the small intestines of patients with Crohn\u2019s disease","volume":"322","author":"Ahrenstedt","year":"1990","journal-title":"N. Engl. J. 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Immunol."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/0016-5085(90)90343-Y","article-title":"Epithelial deposition of Immunoglobulin G1 and activated complement (C3b and Terminal Complement Complex) in ulcerative colitis","volume":"98","author":"Halstensen","year":"1990","journal-title":"Gastroenterology"},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"3887","DOI":"10.4049\/jimmunol.167.7.3887","article-title":"Intestinal trefoil factor induces decay-accelerating factor expression and enhances the protective activities against complement activation in intestinal epithelial cells","volume":"167","author":"Andoh","year":"2001","journal-title":"J. Immunol."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1084\/jem.20030380","article-title":"Antiadhesive role of apical decay-accelerating factor (CD55) in human neutrophil transmigration across mucosal epithelia","volume":"198","author":"Lawrence","year":"2003","journal-title":"J. Exp. Med."},{"key":"2023033006292969300_","doi-asserted-by":"crossref","first-page":"3836","DOI":"10.4049\/jimmunol.172.6.3836","article-title":"Decay-accelerating factor deficiency increases susceptibility to dextran sulfate sodium-induced colitis: role for complement in inflammatory bowel disease","volume":"172","author":"Lin","year":"2004","journal-title":"J. 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