Phenotypic variations in resting and activated levels of ICAM-1 expression by cultured human aortic endothelial cells.
ICAM-1 is an inducible glycoprotein important in the adhesion, activation, and transmigration of circulating leukocytes across the vascular endothelial monolayer, and it likely plays a key role in the allogeneic response. To determine the reproducibility and significance of variations in resting levels of cell surface ICAM-1, 3 individual measurements of ICAM-1 levels were performed on 26 individual isolates of human aortic endothelial cells (HAECs) both at rest and following activation by allogeneic lymphocytes, using flow cytometry. Resting HAEC ICAM-1 levels varied 10-fold (range 6-60 mean fluorescence channels) depending on the isolate studied. There were strong correlations (r = 0.71 to 0.77, P < 0.0001) between the three measurements (performed no closer than weekly intervals on separate cultures), attesting to the consistency of the phenotypic expression. Constitutive expression of ICAM-1 was not affected by cell age, based upon comparing a subset of these isolates across 3 population doublings. Levels of HAEC ICAM-1 following allogeneic lymphocyte activation varied 15-fold (range 20-300 mean fluorescent channels) and, more important, correlated with resting ICAM-1 levels (r = 0.58, P = 0.002). Finally, constitutive ICAM-1 expression was related to TNF-alpha-induced ICAM-1 levels based upon a subset of the isolates studied. These data suggest that phenotypic, and likely genetic, differences in quiescent endothelial cell adhesion molecule expression can influence inflammatory responses including alloresponsiveness to the vasculature.
Everett
J P
JP
Department of Medicine, Oregon Health Sciences University, Portland.
Shipley
G D
GD
Mauck
K A
KA
Wagner
C R
CR
Morris
T E
TE
Hosenpud
J D
JD
D001011:Aorta; D002478:Cells, Cultured / Q000737:chemistry; D016922:Cellular Senescence; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology*; D014644:Genetic Variation; D016027:Heart Transplantation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis* / Q000235:genetics*; D009000:Monocytes / Q000502:physiology; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1