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Cell surface receptors play an essential role in neutrophil and macrophage functions. The same receptor can provide different outcomes within diverse leukocyte subsets in different inflammatory conditions. Understanding the variety of responses mediated by one receptor is critical for the development of anti-inflammatory treatments. In this study, we evaluated the role of a leukocyte adhesive receptor, integrin \u03b1D\u03b22, in the development of acute inflammation. \u03b1D\u03b22 is mostly expressed on macrophages and contributes to the development of chronic inflammation. In contrast, we found that \u03b1D-knockout dramatically increases mortality in the cecal ligation and puncture sepsis model and LPS-induced endotoxemia. This pathologic outcome of \u03b1D-deficient mice is associated with a reduced number of monocyte-derived macrophages and an increased number of neutrophils in their lungs. However, the tracking of adoptively transferred fluorescently labeled wild-type (WT) and \u03b1D\u2212\/\u2212 monocytes in WT mice during endotoxemia demonstrated only a moderate difference between the recruitment of these two subsets. Moreover, the rescue experiment, using i.v. injection of WT monocytes to \u03b1D-deficient mice followed by LPS challenge, showed only slightly reduced mortality. Surprisingly, the injection of WT neutrophils to the bloodstream of \u03b1D\u2212\/\u2212 mice markedly increased migration of monocyte-derived macrophage to lungs and dramatically improves survival. \u03b1D-deficient neutrophils demonstrate increased necrosis\/pyroptosis. \u03b1D\u03b22-mediated macrophage accumulation in the lungs promotes efferocytosis that reduced mortality. Hence, integrin \u03b1D\u03b22 implements a complex defense mechanism during endotoxemia, which is mediated by macrophages via a neutrophil-dependent pathway.<\/jats:p>","DOI":"10.1002\/jlb.3hi0820-529rr","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T11:56:29Z","timestamp":1610711789000},"page":"877-890","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Frontline Science: The expression of integrin \u03b1D\u03b22 (CD11d\/CD18) on neutrophils orchestrates the defense mechanism against endotoxemia and sepsis"],"prefix":"10.1093","volume":"109","author":[{"given":"William P","family":"Bailey","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Ardell","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasey R","family":"Keever","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego J","family":"Rodriguez-Gil","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy R","family":"Ozment","sequence":"additional","affiliation":[{"name":"Department of Surgery, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"},{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Surgery, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"},{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin P","family":"Yakubenko","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"},{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University , Johnson City, Tennessee , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"issue":"6342","key":"2023032108265133500_jlb10868-cit-0001","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1126\/science.aam7928","article-title":"Inflammation and metabolism in tissue 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