{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:48:26Z","timestamp":1787161706157,"version":"build-2736575974"},"reference-count":47,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:p>\n                    Acute lung injury (ALI) still poses a major challenge in critical care medicine. Neutrophils, platelets, and chemokines are all considered key components in the development of ALI. The Duffy antigen receptor for chemokines (DARC ) is thought to be involved in scavenging, transendothelial transport, and presentation of neutrophil-specific chemokines. DARC is expressed on endothelial cells and erythrocytes but not on leukocytes. Here, we show that DARC is crucial for chemokine-mediated leukocyte recruitment in vivo. However, we also demonstrate that changes in chemokine and chemokine receptor homeostasis, associated with Darc gene deficiency, exert strong anti-inflammatory effects. Neutrophils from Darc gene-deficient ( Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    ) mice display a more prolonged downregulation of CXCR2 during severe inflammation than neutrophils from wild-type mice. In a CXCR2-dependent model of acid-induced ALI, Darc gene deficiency prevents ALI. Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    mice demonstrate fully preserved oxygenation, only a small increase in vascular permeability, and a complete lack of pulmonary neutrophil recruitment. Further analysis reveals that only neutrophils but neither endothelial cells nor erythrocytes from Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    mice confer protection from ALI. The protection appears to be due to abolished pulmonary recruitment of neutrophils from Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    mice. The generation of neutrophil-platelet aggregates, a key mechanism in both pulmonary neutrophil recruitment and thrombus formation, is also affected by altered CXCR2 homeostasis in Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    mice. CXCR2 blockade enhances the formation of platelet-neutrophil aggregates and thereby corrects a formerly unknown bleeding defect in Darc\n                    <jats:sup>\u2212\/ \u2212<\/jats:sup>\n                    mice. In summary, our study suggests that chemokine\/chemokine receptor homeostasis plays a previously unrecognized and crucial role in severe ALI.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00224.2009","type":"journal-article","created":{"date-parts":[[2010,1,8]],"date-time":"2010-01-08T21:49:41Z","timestamp":1262987381000},"page":"L462-L471","source":"Crossref","is-referenced-by-count":27,"title":["Chemokine homeostasis vs. chemokine presentation during severe acute lung injury: the other side of the Duffy antigen receptor for chemokines"],"prefix":"10.1152","volume":"298","author":[{"given":"Alexander","family":"Zarbock","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, University of M\u00fcnster and"},{"name":"Max-Planck Institute of Molecular Biomedicine, M\u00fcnster, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Bishop","sequence":"additional","affiliation":[{"name":"The 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