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A central regulator of leukocyte recruitment is Rac1. In this study, we analyzed the effects of the RacGAP ArhGAP15 on leukocyte recruitment. Using ArhGAP15-deficient mice, reduced neutrophil adhesion and transmigration in the TNF-\u03b1\u2013inflamed cremaster muscle and a prolongation of chemokine-dependent leukocyte adhesion could be observed. In a murine model of sterile kidney injury, reduced neutrophil infiltration, and serum creatinine levels were apparent. Further in vitro and in vivo analyses revealed a defective intravascular crawling capacity, resulting from increased affinity of the \u03b22-integrin Mac-1 after prolonged chemokine stimulation of neutrophils. LFA-1 activity regulation was not affected. Summarizing, ArhGAP15 specifically regulates Mac-1, but not LFA-1, and affects leukocyte recruitment by controlling postadhesion strengthening and intravascular crawling in a Mac-1\u2013dependent manner. In conclusion, ArhGAP15 is involved in the time-dependent regulation of leukocyte postadhesion in sterile inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.2000047","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T01:25:32Z","timestamp":1598318732000},"page":"1365-1375","source":"Crossref","is-referenced-by-count":15,"title":["ArhGAP15, a RacGAP, Acts as a Temporal Signaling Regulator of Mac-1 Affinity in Sterile Inflammation"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6539-6478","authenticated-orcid":false,"given":"Andreas","family":"Margraf","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster , 48149 Muenster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anika","family":"Cappenberg","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster , 48149 Muenster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Vadillo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster , 48149 Muenster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5910-1277","authenticated-orcid":false,"given":"Nadine","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster , 48149 Muenster ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Muenster , 48149 Muenster 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