title: Chemokine RANTES in severe pulmonary arterial hypertension.
abstract: The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.
authors.affiliation: Center for Pulmonary Vascular Diseases, UPRES EA 2705, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.forename: Véronique
authors.initials: V
authors.lastname: Zarka
authors.forename: Ingrid
authors.initials: I
authors.lastname: Durand-Gasselin
authors.forename: Gianpaola
authors.initials: G
authors.lastname: Monti
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
authors.forename: Gilles
authors.initials: G
authors.lastname: Garcia
authors.forename: Frédérique
authors.initials: F
authors.lastname: Capron
authors.forename: Aurore
authors.initials: A
authors.lastname: Coulomb-Lherminé
authors.forename: Anne
authors.initials: A
authors.lastname: Marfaing-Koka
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Dominique
authors.initials: D
authors.lastname: Emilie
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D018946:Chemokine CCL5; D012333:RNA, Messenger