title: Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH.
  
  
  OBJECTIVE
  To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted lungs of patients with idiopathic PAH versus healthy donor lungs and to demonstrate functional relevance by blocking stromal-derived factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary hypertension in rats.
  
  
  METHODS
  Immunohistochemistry was performed on lung tissue sections from patients with idiopathic PAH and healthy donors. All positively stained cells in whole-lung tissue sections, surrounding the vessels, and in the different compartments of the vessels were counted. To study the effects of blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration.
  
  
  RESULTS
  We found a significant increase of the perivascular number of macrophages (CD68(+)), macrophages/monocytes (CD14(+)), mast cells (toluidine blue(+)), dendritic cells (CD209(+)), T cells (CD3(+)), cytotoxic T cells (CD8(+)), and helper T cells (CD4(+)) in vessels of idiopathic PAH lungs compared with control subjects. FoxP3(+) mononuclear cells were significantly decreased. In the monocrotaline model, the NOX-A12-induced reduction of mast cells, CD68(+) macrophages, and CD3(+) T cells was associated with improvement of hemodynamics and pulmonary vascular remodeling.
  
  
  CONCLUSIONS
  Our findings reveal altered perivascular inflammatory cell infiltration in pulmonary vascular lesions of patients with idiopathic pulmonary arterial hypertension. Targeting attraction of inflammatory cells by blocking stromal-derived factor-1 may be a novel approach for treatment of PAH.
authors.affiliation: Pulmonary Pharmacotherapy, Universities of Giessen and Marburg Lung Center, Aulweg 130, Giessen, Germany.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Savai
authors.forename: Soni S
authors.initials: SS
authors.lastname: Pullamsetti
authors.forename: Julia
authors.initials: J
authors.lastname: Kolbe
authors.forename: Ewa
authors.initials: E
authors.lastname: Bieniek
authors.forename: Robert
authors.initials: R
authors.lastname: Voswinckel
authors.forename: Ludger
authors.initials: L
authors.lastname: Fink
authors.forename: Axel
authors.initials: A
authors.lastname: Scheed
authors.forename: Christin
authors.initials: C
authors.lastname: Ritter
authors.forename: Bhola K
authors.initials: BK
authors.lastname: Dahal
authors.forename: Axel
authors.initials: A
authors.lastname: Vater
authors.forename: Sven
authors.initials: S
authors.lastname: Klussmann
authors.forename: Hossein A
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Norbert
authors.initials: N
authors.lastname: Weissmann
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Gamal A
authors.initials: GA
authors.lastname: Banat
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D000818:Animals; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D051381:Rats; D046509:Tissue Culture Techniques; D055815:Young Adult