{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:39:21Z","timestamp":1791247161772,"version":"4.1.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2004,3,1]],"date-time":"2004-03-01T00:00:00Z","timestamp":1078099200000},"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":[[2004,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Some suggest that sickle cell disease (SCD) is associated with a \u201cproinflammatory state\u201d that predisposes patients to acute chest syndrome in the setting of triggering factors. Conflicting data emerged when inflammation markers in SCD were compared with healthy individuals. Therefore, we examined transgenic sickle and control mice at baseline and with endotoxin (LPS) intraperitoneal injection to determine whether a proinflammatory state truly exists. At baseline, sickle mice had elevated levels of circulating leukocytes and soluble vascular cell adhesion molecule 1 (sVCAM-1). No other differences were observed at baseline or in response to saline. However, LPS challenge was associated with significant increases in mortality (p &amp;lt; 0.05), airway tone (p &amp;lt; 0.03), serum and bronchoalveolar lavage levels of cytokines tumor necrosis factor-\u03b1 (p &amp;lt; 0.03), interleukin-1\u03b2 (p &amp;lt; 0.02), and sVCAM-1 (p &amp;lt; 0.01) in sickle mice compared with control subjects. Furthermore, 4 hours after LPS, microarray analysis identified 413 genes differentially expressed in the sickle mice (n = 5) compared with only 7 in the control subjects (n = 5). No difference in lung parenchyma was observed by light microscopy. This enhanced response to LPS suggests that the sickle red blood cell confers a subclinical \u201cproinflammatory state.\u201d This enhanced response to inflammatory insult, particularly by adhesion molecules such as sVCAM-1, could play a role in the increased susceptibility to pulmonary dysfunction that has been observed clinically in SCD.<\/jats:p>","DOI":"10.1164\/rccm.200302-224oc","type":"journal-article","created":{"date-parts":[[2003,12,22]],"date-time":"2003-12-22T20:23:36Z","timestamp":1072124616000},"page":"687-695","source":"Crossref","is-referenced-by-count":51,"title":["Enhanced Pulmonary and Systemic Response to Endotoxin in Transgenic Sickle Mice"],"prefix":"10.1093","volume":"169","author":[{"given":"J. David","family":"Holtzclaw","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology\/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Jack","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology\/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Aguayo","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology\/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Eckman","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology\/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Roman","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Bone Marrow Transplantation, Department of Pediatrics, Emory University School of Medicine; Division of Medicine, Atlanta Veterans Affairs Medical Center, Morehouse School of Medicine; Winship Cancer Institute, Hematology\/Oncology Department, Emory University School of Medicine; and Division of Pulmonary, Allergy, and Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis L.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology and Bone 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