{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:09:03Z","timestamp":1774069743352,"version":"3.50.1"},"reference-count":50,"publisher":"American Society of Hematology","issue":"10","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug targeting to a highly expressed, noninternalizable determinant up-regulated on the perturbed endothelium may help to manage inflammation and thrombosis. We tested whether inter-cellular adhesion molecule-1 (ICAM-1) targeting is suitable to deliver antithrombotic drugs to the pulmonary vascular lumen. ICAM-1 antibodies bind to the surface of endothelial cells in culture, in perfused lungs, and in vivo. Proinflammatory cytokines enhance anti-ICAM binding to the endothelium without inducing internalization. 125I-labeled anti-ICAM and a reporter enzyme (\u03b2-Gal) conjugated to anti-ICAM bind to endothelium and accumulate in the lungs after intravenous administration in rats and mice. Anti-ICAM is seen to localize predominantly on the luminal surface of the pulmonary endothelium by electron microscopy. We studied the pharmacological effect of ICAM-directed targeting of tissue-type plasminogen activator (tPA). Anti-ICAM\/tPA, but not control IgG\/tPA, conjugate accumulates in the rat lungs, where it exerts plasminogen activator activity and dissolves fibrin microemboli. Therefore, ICAM may serve as a target for drug delivery to endothelium, for example, for pulmonary thromboprophylaxis. Enhanced drug delivery to sites of inflammation and the potential anti-inflammatory effect of blocking ICAM-1 may enhance the benefit of this targeting strategy.<\/jats:p>","DOI":"10.1182\/blood-2002-09-2853","type":"journal-article","created":{"date-parts":[[2003,5,5]],"date-time":"2003-05-05T19:24:00Z","timestamp":1052162640000},"page":"3977-3984","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":83,"title":["ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface"],"prefix":"10.1182","volume":"101","author":[{"given":"Juan-Carlos","family":"Murciano","sequence":"first","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Muro","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Koniaris","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melpo","family":"Christofidou-Solomidou","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Harshaw","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven M.","family":"Albelda","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Neil","family":"Granger","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas B.","family":"Cines","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA; and the Department of Physiology, Louisiana State University, Shreveport, LA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir R.","family":"Muzykantov","sequence":"additional","affiliation":[{"name":"From the Institute of Environmental Medicine, Department of Pharmacology, Department of 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