Dendritic cell recruitment in lesions of human and experimental pulmonary hypertension

¹ 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 11, Clamart, France; and Institut National de la Santé et de la Recherche Médicale, U764, Institut Fédératif de Recherche 13, Clamart, France
² 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 11, Clamart, France
³ Institut National de la Santé et de la Recherche Médicale, U764, Institut Fédératif de Recherche 13, Clamart, France
⁴ UPRES EA2705, Laboratoire de Chirurgie Expérimentale, Centre Chirurgical Marie Lannelongue, Université Paris-Sud 11, Le Plessis Robinson, France
⁵ 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 11, Clamart, France; and UPRES EA2705, Laboratoire de Chirurgie Expérimentale, Centre Chirurgical Marie Lannelongue, Université Paris-Sud 11, Le Plessis Robinson, France

^* To whom correspondence should be addressed. E-mail: marc.humbert{at}abc.aphp.fr.

	Abstract

We have tested the hypothesis that dendritic cells (DCs), key players in immunity and tolerance, might be involved in the immunopathology of idiopathic pulmonary arterial hypertension (IPAH).

DCs phenotype and localization were characterized by immunohistochemistry and double-labeling immunofluorescence in lung samples from controls, human IPAH and experimental pulmonary hypertension (monocrotaline-exposed rats).

As compared to controls, morphometric analysis demonstrated increased numbers of DC-SIGN positive cells in muscular pulmonary arteries in IPAH and monocrotaline-induced pulmonary hypertension. In human samples, mean (±SEM) number of DC-SIGN positive cells per artery of 100-300 µm diameter was 1.4±0.4 in controls versus 26.4±2.7 in IPAH (p<0.001). In rats, mean (±SEM) number of OX-62 positive cells per artery of 50-150 µm 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 (p<0.001). Human complex lesions of muscular pulmonary arteries showed transmural DC infiltration. Phenotyping revealed an immature DC profile in human and experimental pulmonary hypertension.

Our results support the concept that immature DCs accumulate in remodeled pulmonary vessels and hence could be involved in the immunopathology of pulmonary hypertension.

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