American Journal of Respiratory and Critical Care Medicine Vol 165. pp. 1419-1425, (2002)
© 2002 American Thoracic Society
CX3C Chemokine Fractalkine in Pulmonary Arterial Hypertension
Karl Balabanian,
Arnaud Foussat,
Peter Dorfmüller,
Ingrid Durand-Gasselin,
Francis Capel,
Laurence Bouchet-Delbos,
Alain Portier,
Anne Marfaing-Koka,
Roman Krzysiek,
Anne-Cécile Rimaniol,
Gérald Simonneau,
Dominique Emilie and
Marc Humbert
INSERM U131, UPRES EA2705, Centre des Maladies Vasculaires Pulmonaires, Service de Pneumologie et Réanimation Respiratoire; and Service d'Hématologie, Institut Paris-Sud sur les Cytokines, Hôpital Antoine-Béclère, Université Paris-Sud, Assistance Publique-Hôpitaux de Paris, Clamart, France
Correspondence and requests for reprints should be addressed to Marc Humbert, Service de Pneumologie, Hôpital Antoine-Béclère, 157, Rue de la Porte de Trivaux, 92140 Clamart, France. E-mail: humbert{at}ipsc.u-psud.fr
Perivascular infiltrates composed of macrophages and lymphocytes have been described in lung biopsies of patients displaying pulmonary arterial hypertension (PAH), suggesting that circulating inflammatory cells can be recruited in affected vessels. CX3C chemokine fractalkine is produced by endothelial cells and promotes leukocyte recruitment, but unlike other chemokines, it can capture leukocytes rapidly and firmly in an integrin-independent manner under high blood flow. We therefore hypothesized that fractalkine may contribute to pulmonary inflammatory cell recruitment in PAH. Expression and function of the fractalkine receptor (CX3CR1) were studied by use of triple-color flow cytometry on circulating T-lymphocyte subpopulations in freshly isolated peripheral blood mononuclear cells from control subjects and patients with PAH. Plasma-soluble fractalkine concentrations were measured by enzyme-linked immunosorbent assay. Finally, fractalkine mRNA and protein expression were analyzed in lung samples by reverse transcriptase-polymerase chain reaction or in situ hybridization and immunohistochemistry, respectively. In patients with PAH, CX3CR1 expression and function are upregulated in circulating T-lymphocytes, mostly of the CD4+ subset, and plasma soluble fractalkine concentrations are elevated, as compared with control subjects. Fractalkine mRNA and protein product are expressed in pulmonary artery endothelial cells. We conclude that inflammatory mechanisms involving chemokine fractalkine and its receptor CX3CR1 may have a role in the natural history of PAH.
Key Words: chemokines • endothelium-derived factors • fractalkine • pulmonary hypertension • receptors
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