{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:23:05Z","timestamp":1760646185749,"version":"3.40.3"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2007,4,1]],"date-time":"2007-04-01T00:00:00Z","timestamp":1175385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The Src homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) is an adaptor molecule critical for immunoreceptor and integrin signaling in multiple hemopoietic lineages. We showed previously that SLP-76 is required for neutrophil function in vitro, including integrin-induced adhesion and production of reactive oxygen intermediates, and to a lesser extent, Fc\u03b3R-induced calcium flux and reactive oxygen intermediate production. It has been difficult to determine whether SLP-76 regulates neutrophil responses in vivo, because Slp-76\u2212\/\u2212 mice exhibit marked defects in thymocyte and vascular development, as well as platelet and mast cell function. To circumvent these issues, we generated mice with targeted loss of SLP-76 expression within myeloid cells. Neutrophils obtained from these animals failed to respond to integrin activation in vitro, similar to Slp-76\u2212\/\u2212 cells. Despite these abnormalities, SLP-76-deficient neutrophils migrated normally in vivo in response to Staphylococcus aureus infection and efficiently cleared micro-organisms. Interestingly, SLP-76-deficient neutrophils did not induce a robust inflammatory response in the localized Shwartzman reaction. Collectively, these data suggest that disruption of integrin signaling via loss of SLP-76 expression differentially impairs neutrophil functions in vivo, with preservation of migration and killing of S. aureus but reduction in LPS-induced tissue damage and vascular injury.<\/jats:p>","DOI":"10.4049\/jimmunol.178.7.4606","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T22:53:35Z","timestamp":1397861615000},"page":"4606-4614","source":"Crossref","is-referenced-by-count":23,"title":["Loss of SLP-76 Expression within Myeloid Cells Confers Resistance to Neutrophil-Mediated Tissue Damage while Maintaining Effective Bacterial Killing"],"prefix":"10.1093","volume":"178","author":[{"given":"Regina A","family":"Clemens","sequence":"first","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Medical Scientist Training Program, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie E","family":"Lenox","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Division of Oncology, Children\u2019s Hospital of Philadelphia , PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taku","family":"Kambayashi","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Bezman","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Graduate Program in Cell and Molecular Biology, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan S","family":"Maltzman","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Department of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim E","family":"Nichols","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Division of Oncology, Children\u2019s Hospital of Philadelphia , PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary A","family":"Koretzky","sequence":"additional","affiliation":[{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"},{"name":"Department of Medicine, University of Pennsylvania School of Medicine , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,4,1]]},"reference":[{"first-page":"204","volume-title":"Eur. J. Surg.","year":"2002","key":"2025032802441147700_R1"},{"first-page":"1601","volume-title":"J. Immunol.","year":"2001","key":"2025032802441147700_R2"},{"first-page":"182","volume-title":"Gastroenterology","year":"1998","key":"2025032802441147700_R3"},{"first-page":"693","volume-title":"Immunity","year":"2001","key":"2025032802441147700_R4"},{"first-page":"40","volume-title":"Shock","year":"2005","key":"2025032802441147700_R5"},{"first-page":"7580","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1998","key":"2025032802441147700_R6"},{"first-page":"154","volume-title":"Curr. Opin. Pharmacol.","year":"2004","key":"2025032802441147700_R7"},{"first-page":"115","volume-title":"Semin. Immunol.","year":"2002","key":"2025032802441147700_R8"},{"first-page":"172","volume-title":"Inflamm. Bowel Dis.","year":"2006","key":"2025032802441147700_R9"},{"first-page":"5029","volume-title":"J. Immunol.","year":"1999","key":"2025032802441147700_R10"},{"first-page":"G1125","volume-title":"Am. J. Physiol.","year":"1999","key":"2025032802441147700_R11"},{"first-page":"1855","volume-title":"FASEB J.","year":"1999","key":"2025032802441147700_R12"},{"first-page":"3573","volume-title":"Blood","year":"2006","key":"2025032802441147700_R13"},{"first-page":"825","volume-title":"Annu. Rev. Immunol.","year":"2002","key":"2025032802441147700_R14"},{"first-page":"379","volume-title":"Semin. Immunol.","year":"2004","key":"2025032802441147700_R15"},{"first-page":"416","volume-title":"Science","year":"1998","key":"2025032802441147700_R16"},{"first-page":"413","volume-title":"Science","year":"1998","key":"2025032802441147700_R17"},{"first-page":"19","volume-title":"J. Clin. Invest.","year":"1999","key":"2025032802441147700_R18"},{"first-page":"12056","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2000","key":"2025032802441147700_R19"},{"first-page":"1737","volume-title":"J. Clin. Invest.","year":"1999","key":"2025032802441147700_R20"},{"first-page":"5916","volume-title":"J. Biol. Chem.","year":"2001","key":"2025032802441147700_R21"},{"first-page":"705","volume-title":"J. Exp. Med.","year":"2002","key":"2025032802441147700_R22"},{"first-page":"761","volume-title":"Immunity","year":"2003","key":"2025032802441147700_R23"},{"first-page":"247","volume-title":"Science","year":"2003","key":"2025032802441147700_R24"},{"first-page":"95","volume-title":"Immunity","year":"2003","key":"2025032802441147700_R25"},{"first-page":"1243","volume-title":"J. Exp. Med.","year":"2003","key":"2025032802441147700_R26"},{"first-page":"271","volume-title":"Immunity","year":"2006","key":"2025032802441147700_R27"},{"first-page":"893","volume-title":"J. Exp. Med.","year":"2005","key":"2025032802441147700_R28"},{"first-page":"14602","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1997","key":"2025032802441147700_R29"},{"first-page":"265","volume-title":"Transgenic Res.","year":"1999","key":"2025032802441147700_R30"},{"first-page":"895","volume-title":"J. Cell Biol.","year":"1996","key":"2025032802441147700_R31"},{"first-page":"1120","volume-title":"J. Immunol.","year":"1999","key":"2025032802441147700_R32"},{"first-page":"1826","volume-title":"Mol. Cell. Biol.","year":"2006","key":"2025032802441147700_R33"},{"first-page":"5652","volume-title":"J. Immunol.","year":"2003","key":"2025032802441147700_R34"},{"first-page":"93","volume-title":"Immunity","year":"2005","key":"2025032802441147700_R35"},{"first-page":"623","volume-title":"Immunity","year":"2004","key":"2025032802441147700_R36"},{"first-page":"39","volume-title":"Immunity","year":"1999","key":"2025032802441147700_R37"},{"first-page":"259","volume-title":"J. Clin. Invest.","year":"1992","key":"2025032802441147700_R38"},{"first-page":"273","volume-title":"Proc. Soc. Exp. Biol. Med.","year":"1964","key":"2025032802441147700_R39"},{"first-page":"167","volume-title":"Exp. Toxicol. Pathol.","year":"1995","key":"2025032802441147700_R40"},{"first-page":"621","volume-title":"Cell. Signal.","year":"1999","key":"2025032802441147700_R41"},{"first-page":"13867","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2004","key":"2025032802441147700_R42"},{"first-page":"93","volume-title":"Immunity","year":"1998","key":"2025032802441147700_R43"},{"first-page":"547","volume-title":"Immunity","year":"2002","key":"2025032802441147700_R44"},{"first-page":"1340","volume-title":"J. Clin. Invest.","year":"1997","key":"2025032802441147700_R45"},{"first-page":"404","volume-title":"Am. J. Pathol.","year":"1985","key":"2025032802441147700_R46"},{"first-page":"887","volume-title":"Int. Immunol.","year":"2000","key":"2025032802441147700_R47"},{"first-page":"541","volume-title":"J. Leukocyte Biol.","year":"2004","key":"2025032802441147700_R48"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/178\/7\/4606\/62654521\/zim00707004606.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/178\/7\/4606\/62654521\/zim00707004606.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T20:28:28Z","timestamp":1743366508000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/178\/7\/4606\/8023531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4,1]]},"references-count":48,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2007,4,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.178.7.4606","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"type":"print","value":"0022-1767"},{"type":"electronic","value":"1550-6606"}],"subject":[],"published-other":{"date-parts":[[2007,4]]},"published":{"date-parts":[[2007,4,1]]}}}