title: PECAM-1 polymorphism affects monocyte adhesion to endothelial cells.
abstract: BACKGROUND
  Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) plays an important role in leukocyte-endothelial cell adhesion and transmigration. Single nucleotide polymorphisms of PECAM-1 encoding amino acid substitutions at positions 98 leucine/valine (L/V), 536 serine/asparagine (S/N), and 643 arginine/glycine (R/G) occur in strong genetic linkage resulting in two common haplotypes (LSR and VNG). These PECAM-1 polymorphisms are associated with graft-versus-host disease after hematopoietic stem cell transplantation and with cardiovascular disease, but whether they influence PECAM-1 function is unknown.
  
  
  METHODS
  We examined the effect of homozygous and heterozygous expression of the PECAM-1 LSR and VNG genotypes on the adhesive interactions of peripheral blood monocytes and activated endothelial cell monolayers under shear stress in a flow-based cell adhesion assay.
  
  
  RESULTS
  There was no difference in monocyte adhesion between the two homozygous genotypes of PECAM-1 but when monocytes expressed both alleles in heterozygous form, firm adhesion of monocytes to endothelial cells was markedly increased. PECAM-1 polymorphism expressed in homozygous or heterozygous form by endothelial cells did not influence monocyte adhesion.
  
  
  CONCLUSIONS
  This is, to our knowledge, the first demonstration that PECAM-1 genotype can alter the level of monocyte binding to endothelial cells and a demonstration that heterozygous expression of a polymorphic protein may lead to altered function.
authors.affiliation: Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom. reyna.goodman@addenbrookes.nhs.uk
authors.forename: Reyna S
authors.initials: RS
authors.lastname: Goodman
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Kirton
authors.forename: Gertie J
authors.initials: GJ
authors.lastname: Oostingh
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.forename: Michael R
authors.initials: MR
authors.lastname: Clark
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Taylor
mesh_terms: D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1