{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:19:46Z","timestamp":1792095586455,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"French National Institute for Health and Medical Research and French National Agency for Research","award":["ANR-12-JSV1-0004-01"],"award-info":[{"award-number":["ANR-12-JSV1-0004-01"]}]},{"DOI":"10.13039\/501100011879","name":"LabEx LERMIT","doi-asserted-by":"publisher","award":["ANR-10-LABX-0033-LERMIT"],"award-info":[{"award-number":["ANR-10-LABX-0033-LERMIT"]}],"id":[{"id":"10.13039\/501100011879","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Inflammation and endothelial dysfunction are considered two primary instigators of pulmonary arterial hypertension (PAH). CD74 is a receptor for the proinflammatory cytokine macrophage migration inhibitory factor (MIF). This ligand\/receptor complex initiates survival pathways and cell proliferation, and it triggers the synthesis and secretion of major proinflammatory factors and cell adhesion molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We hypothesized that the MIF\/CD74 signaling pathway is overexpressed in idiopathic PAH (iPAH) and contributes to a proinflammatory endothelial cell (EC) phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Primary early passage cultures of human ECs isolated from lung tissues obtained from patients with iPAH and controls were examined for their ability to secrete proinflammatory mediators and bind inflammatory cells with or without modulation of the functional activities of the MIF\/CD74 complex. In addition, we tested the efficacies of curative treatments with either the MIF antagonist ISO-1 or anti-CD74 neutralizing antibodies on the aberrant proinflammatory EC phenotype in vitro and in vivo and on the progression of monocrotaline-induced pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>In human lung tissues, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expressions are markedly up-regulated in the endothelium of distal iPAH pulmonary arteries. Circulating MIF levels are increased in the serum of patients with PAH compared with control subjects, and T-cell lymphocytes represent a source of this overabundance. In addition, CD74 is highly expressed in the endothelium of muscularized pulmonary arterioles and in cultured pulmonary ECs from iPAH, contributing to an exaggerated recruitment of peripheral blood mononuclear cells to pulmonary iPAH ECs. Finally, we found that curative treatments with the MIF antagonist ISO-1 or anti-CD74 neutralizing antibodies partially reversed development of pulmonary hypertension in rats and substantially reduced inflammatory cell infiltration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We report here that CD74 and MIF are markedly increased and activated in patients with iPAH, contributing to the abnormal proinflammatory phenotype of pulmonary ECs in iPAH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201402-0322oc","type":"journal-article","created":{"date-parts":[[2015,7,23]],"date-time":"2015-07-23T14:08:37Z","timestamp":1437660517000},"page":"983-997","source":"Crossref","is-referenced-by-count":196,"title":["Proinflammatory Signature of the Dysfunctional Endothelium in Pulmonary Hypertension. Role of the Macrophage Migration Inhibitory Factor\/CD74 Complex"],"prefix":"10.1093","volume":"192","author":[{"given":"Morane","family":"Le Hiress","sequence":"first","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-5099","authenticated-orcid":false,"given":"Ly","family":"Tu","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Ricard","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Phan","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Thuillet","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Fadel","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Dorfm\u00fcller","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5110-9194","authenticated-orcid":false,"given":"David","family":"Montani","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 Paris-Sud and Universit\u00e9 Paris-Saclay, School of M\u00e9decine, Kremlin-Bic\u00eatre, France"},{"name":"AP-HP, Service de Pneumologie, Centre de R\u00e9f\u00e9rence de l\u2019Hypertension Pulmonaire S\u00e9v\u00e8re, DHU Thorax Innovation, H\u00f4pital de Bic\u00eatre, Kremlin-Bic\u00eatre, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"de Man","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, VU University Medical Center\/Institute of Cardiovascular Research, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-2892","authenticated-orcid":false,"given":"Marc","family":"Humbert","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, LabEx LERMIT, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France"},{"name":"Universit\u00e9 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