title: Lymph angiogenesis after lung transplantation and relation to acute organ rejection in humans.
abstract: BACKGROUND
  Acute rejection after kidney transplantation was found to be associated with increased recipient-derived lymph angiogenesis. However, the relation of lymph angiogenesis to acute rejection in lung transplantation has not yet been investigated.
  
  
  METHODS
  Transbronchial biopsies from 23 lung transplant recipients (47 + or - 15 years old, 15 male, 19 double lungs, 4 single lungs), taken at 14 and 90 days after transplantation were investigated. Immunohistostaining for PROX-1 (an lymphatic endothelial marker) and for vascular endothelial growth factor receptor (VEGFR) 1 and 2 (blood capillary markers) was performed. Biopsies with no sign of rejection (International Society for Heart and Lung Transplantation [ISHLT] grade A0, n = 27) were compared with biopsies with rejection grade A1/A2 (n = 19).
  
  
  RESULTS
  Biopsies with ISHLT rejection grade A1 or A2 showed a significantly higher density of PROX-1 marked lymphatics in comparison with biopsies of grade A0 at 14 days (p < 0.001) and at 90 days (p < 0.001) after transplantation, and in the collective comparison (all biopsies with ISHLT grade A1 or A2 versus all biopsies with grade A0, p < 0.001). For VEGFR-1 and VEGFR-2, no difference was found between ISHLT grade A1 or A2 compared with grade A0, neither at 14 or 90 days nor in the collective comparison.
  
  
  CONCLUSIONS
  Increased lymphatic angiogenesis after lung transplantation, demonstrated by increased density of the PROX-1 lymphatic endothelial marker, was associated with histologically evident acute organ rejection in humans. Although the exact role of lymphatic angiogenesis in acute organ rejection remains to be determined, further study of the interaction between the microvasculature and acute rejection seems warranted. Pending further investigation, analysis of PROX-1 density may develop into a new tool for rejection monitoring, supplementing conventional rejection grading.
authors.affiliation: Department of Cardiovascular Surgery, Freiburg University Medical Centre, Freiburg, Germany. alexey.dashkevich@uniklinik-freiburg.de
authors.forename: Alexey
authors.initials: A
authors.lastname: Dashkevich
authors.forename: Claudia
authors.initials: C
authors.lastname: Heilmann
authors.forename: Gian
authors.initials: G
authors.lastname: Kayser
authors.forename: Martin
authors.initials: M
authors.lastname: Germann
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Bernward
authors.initials: B
authors.lastname: Passlick
authors.forename: Hans Joachim
authors.initials: HJ
authors.lastname: Geissler
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D016040:Lung Transplantation; D042583:Lymphangiogenesis; D008297:Male; D008875:Middle Aged; D055815:Young Adult