{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:56:51Z","timestamp":1790333811561,"version":"4.1.0"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2010,9,1]],"date-time":"2010-09-01T00:00:00Z","timestamp":1283299200000},"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":[[2010,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>\u03b22 integrins of neutrophils play a critical role in innate immune defense, but they also participate in tissue destruction during autoimmune inflammation. p190RhoGAP (ArhGAP35), a regulator of Rho family small GTPases, is required for integrin signal transduction in fibroblasts. Prior studies have also suggested a role for p190RhoGAP in \u03b22 integrin signaling in neutrophils. To directly test that possibility, we have generated a novel targeted mutation completely disrupting the p190RhoGAP-encoding gene in mice. p190RhoGAP deficiency led to perinatal lethality and defective neural development, precluding the analysis of neutrophil functions in adult p190RhoGAP\u2212\/\u2212 animals. This was overcome by transplantation of fetal liver cells from p190RhoGAP\u2212\/\u2212 fetuses into lethally irradiated wild-type recipients. Neutrophils from such p190RhoGAP\u2212\/\u2212 bone marrow chimeras developed normally and expressed normal levels of various cell surface receptors. Although p190RhoGAP\u2212\/\u2212 neutrophils showed moderate reduction of \u03b22 integrin-mediated adherent activation, they showed mostly normal migration in \u03b22 integrin-dependent in vitro and in vivo assays and normal \u03b22 integrin-mediated killing of serum-opsonized Staphylococcus aureus and Escherichia coli. A neutrophil- and \u03b22 integrin-dependent transgenic model of the effector phase of autoimmune arthritis also proceeded normally in p190RhoGAP\u2212\/\u2212 bone marrow chimeras. In contrast, all the above responses were completely blocked in CD18\u2212\/\u2212 neutrophils or CD18\u2212\/\u2212 bone marrow chimeras. These results suggest that p190RhoGAP likely does not play a major indispensable role in \u03b22 integrin-mediated in vitro and in vivo neutrophil functions or the effector phase of experimental autoimmune arthritis.<\/jats:p>","DOI":"10.4049\/jimmunol.0904163","type":"journal-article","created":{"date-parts":[[2010,7,31]],"date-time":"2010-07-31T02:12:54Z","timestamp":1280542374000},"page":"3064-3075","source":"Crossref","is-referenced-by-count":35,"title":["Neutrophil Functions and Autoimmune Arthritis in the Absence of p190RhoGAP: Generation and Analysis of a Novel Null Mutation in Mice"],"prefix":"10.1093","volume":"185","author":[{"given":"Tam\u00e1s","family":"N\u00e9meth","sequence":"first","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Futosi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]},{"name":"Department of Medical Chemistry, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Hably","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine R","family":"Brouns","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha M","family":"Jakob","sequence":"additional","affiliation":[{"name":"Walter Brendel Center for Experimental Medicine, Ludwig-Maximilians-University , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Kert\u00e9sz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Walzog","sequence":"additional","affiliation":[{"name":"Walter Brendel Center for Experimental Medicine, Ludwig-Maximilians-University , Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Settleman","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"M\u00f3csai","sequence":"additional","affiliation":[{"name":"Department of Physiology, Semmelweis University School of Medicine , Budapest ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,9,1]]},"reference":[{"key":"2025032411500937700_r1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nri1785","article-title":"Neutrophils and immunity: challenges and opportunities","volume":"6","author":"Nathan","year":"2006","journal-title":"Nat. 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