title: Interleukin-2 alters distribution of CD144 (VE-cadherin) in endothelial cells.
abstract: BACKGROUND
  High-dose IL-2 (HDIL2) is approved for the treatment of metastatic melanoma and renal cell carcinoma, but its use is limited in part by toxicity related to the development of vascular leak syndrome (VLS). Therefore, an understanding of the mechanisms that underlie the initiation and progression of HDIL2-induced increases in endothelial cell (EC) permeability leading to VLS are of clinical importance.
  
  
  METHODS
  We established a novel ex vivo approach utilizing primary human pulmonary microvascular ECs to evaluate EC barrier dysfunction in response to IL-2.
  
  
  RESULTS
  Complementary in vitro studies using exogenous IL-2 and ex vivo studies using serum from patients treated with IL-2 demonstrate that HDIL2 induces VLS through CD144 (vascular endothelial (VE)-cadherin) redistribution.
  
  
  CONCLUSIONS
  These findings provide new insight into how IL-2 induces VLS and identifies VE-cadherin as a potential target for preventing IL-2-related VLS.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Andrew
authors.initials: A
authors.lastname: Zloza
authors.forename: Joseph
authors.initials: J
authors.lastname: Broucek
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.forename: Carl
authors.initials: C
authors.lastname: Ruby
authors.forename: Georges
authors.initials: G
authors.lastname: Samaha
authors.affiliation: Rutgers Cancer Institute of New Jersey, Rutgers University, 195 Little Albany Street, Room 2007, New Brunswick, NJ 08901, USA. howard.kaufman@rutgers.edu.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D051929:CD146 Antigen / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D051929:CD146 Antigen; D017931:DNA Primers; D007376:Interleukin-2; C497902:MCAM protein, human