CX(3)C chemokine fractalkine in pulmonary arterial hypertension.
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. CX(3)C 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 (CX(3)CR1) 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, CX(3)CR1 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 CX(3)CR1 may have a role in the natural history of PAH.
Balabanian
Karl
K
INSERM U131, UPRES EA2705, Centre des Maladies Vasculaires Pulmonaires, Service de Pneumologie et Réanimation Respiratoire, Institut Paris-Sud sur les Cytokines, Hôpital Antoine-Béclère, Université Paris-Sud, Clamart, France.
Foussat
Arnaud
A
Dorfmüller
Peter
P
Durand-Gasselin
Ingrid
I
Capel
Francis
F
Bouchet-Delbos
Laurence
L
Portier
Alain
A
Marfaing-Koka
Anne
A
Krzysiek
Roman
R
Rimaniol
Anne-Cécile
AC
Simonneau
Gérald
G
Emilie
Dominique
D
Humbert
Marc
M
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis* / Q000276:immunology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets
C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D018836:Inflammation Mediators; D008565:Membrane Proteins; D012333:RNA, Messenger