Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension.
In the present study, the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH) was tested. The phenotype and localisation of DCs were characterised by immunohistochemistry and double-labelling immunofluorescence in lung samples from controls, human IPAH patients and an experimental pulmonary hypertension model (monocrotaline-exposed rats). As compared with controls, morphometric analysis demonstrated increased numbers of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (DC-SIGN)-positive cells in muscular pulmonary arteries in IPAH and OX-62-positive DCs in monocrotaline-induced pulmonary hypertension. In human samples, the mean+/-SEM number of DC-SIGN-positive cells.artery(-1) of 100-300 microm diameter was 1.4+/-0.4 in controls versus 26.4+/-2.7 in IPAH. In rats, the number of OX-62-positive cells.artery(-1) of 50-150 microm diameter was 0.5+/-0.2 in controls, and 0.7+/-0.5, 3.1+/-0.5 and 8.4+/-0.6 at day 7, 14 and 28 after monocrotaline exposure, respectively. Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension. The results support the concept that immature dendritic cells accumulate in remodelled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.
Perros
F
F
UPRES EA2705, Service de Pneumologie, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Hôpital Antoine-Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, France.
Dorfmüller
P
P
Souza
R
R
Durand-Gasselin
I
I
Mussot
S
S
Mazmanian
M
M
Hervé
P
P
Emilie
D
D
Simonneau
G
G
Humbert
M
M
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D006976:Hypertension, Pulmonary / Q000276:immunology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D037181:Lectins, C-Type / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D016686:Monocrotaline; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D016686:Monocrotaline; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C459465:OX-62 antigen, rat