PECAM-1 polymorphism affects monocyte adhesion to endothelial cells.
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.
Goodman
Reyna S
RS
Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom. reyna.goodman@addenbrookes.nhs.uk
Kirton
Christopher M
CM
Oostingh
Gertie J
GJ
Schön
Michael P
MP
Clark
Michael R
MR
Bradley
J Andrew
JA
Taylor
Craig J
CJ
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*
D019408:Platelet Endothelial Cell Adhesion Molecule-1