{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:36:14Z","timestamp":1790861774455,"version":"4.1.0"},"reference-count":44,"publisher":"Rockefeller University Press","issue":"7","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,4,2]]},"abstract":"<jats:p>The physiologic role of L-selectin shedding is unknown. Here, we investigate the effect of L-selectin shedding on firm adhesion and transmigration. In a tumor necrosis factor \u03b1\u2013induced model of inflammation, inhibition of L-selectin shedding significantly increased firm adhesion and transmigration by a lymphocyte function\u2013associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1\u2013dependent mechanism. We examined the quality of leukocyte rolling and L-selectin\u2013mediated signaling. Blockade of L-selectin shedding significantly reduced the \u201cjerkiness\u201d of leukocyte rolling, defined as the variability of velocity over time. A low level of jerkiness was also observed in the rolling of microbeads conjugated with L-selectin, a model system lacking the mechanism for L-selectin shedding. Inhibition of L-selectin shedding potentiated activation of LFA-1 and Mac-1 induced by L-selectin cross-linking as shown by activation epitope expression and binding of ICAM-1\u2013conjugated beads. We conclude that inhibition of L-selectin shedding increases leukocyte adhesion and transmigration by (a) increasing leukocyte exposure to the inflamed endothelium by decreasing jerkiness and (b) promoting leukocyte activation by outside-in signaling. These observations help to resolve the apparent discrepancy between the minor contribution of L-selectin to rolling and the significant leukocyte recruitment defect in L-selectin knockout mice.<\/jats:p>","DOI":"10.1084\/jem.193.7.863","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"863-872","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":175,"title":["L-Selectin Shedding Regulates Leukocyte Recruitment"],"prefix":"10.1084","volume":"193","author":[{"given":"Ali","family":"Hafezi-Moghadam","sequence":"first","affiliation":[{"name":"aDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kennard L.","family":"Thomas","sequence":"additional","affiliation":[{"name":"aDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyson J.","family":"Prorock","sequence":"additional","affiliation":[{"name":"aDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Huo","sequence":"additional","affiliation":[{"name":"aDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Ley","sequence":"additional","affiliation":[{"name":"aDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,4,2]]},"reference":[{"key":"2023072509414843600_R1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/0092-8674(91)90279-8","article-title":"Leukocyte-endothelial cell recognitionthree (or more) steps to specificity and diversity","volume":"67","author":"Butcher","year":"1991","journal-title":"Cell."},{"key":"2023072509414843600_R2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.181.2.669","article-title":"Sequential contribution of L- and P-selectin to leukocyte rolling in vivo","volume":"181","author":"Ley","year":"1995","journal-title":"J. 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