Intercellular adhesion molecule-1 (ICAM-1) expression is necessary for monocyte adhesion to the placental bed endothelium and is increased in type 1 diabetic human pregnancy.
BACKGROUND
That adhesion molecule expression is upregulated in endothelial cells of the placental bed in pregnancies complicated by type 1 diabetes mellitus, and that this is associated with increased adherence of peripheral blood monocytes, which can be reversed by reduction in activity or expression of relevant adhesion molecules. Specific aims were to compare the adherence of monocytes from normal pregnancies to decidual endothelial cells from both normal and diabetic pregnancies, and to examine the involvement of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in regulation of such adhesion.


METHODS
We examined adhesion of peripheral blood monocytes (isolated by density gradient centrifugation) of normal third trimester pregnant women, to cultured endothelial cells (isolated from decidual biopsies collected at elective caesarean section) from both normal women and those with type 1 diabetes. Adhesion molecule expression was determined by flow cytometry. The role of ICAM-1 was further investigated by monoclonal antibody-blocking experiments and gene-silencing methodology.


RESULTS
There was a significant increase in monocyte adhesion to decidual endothelial cells from diabetic pregnancies, associated with increased endothelial cell expression of ICAM-1, but not VCAM-1. ICAM-1 expression in normal decidual endothelial cells was stimulated by pro-atherogenic and pro-inflammatory stimuli. Following ICAM-1 antibody blockade, monocyte adhesion was decreased by > 70%. ICAM-1 silencing by small interfering RNAs also inhibited monocyte adhesion and ICAM-1 expression.


CONCLUSIONS
These findings implicate upregulation of ICAM-1 in decidual endothelial cells in the development of placental bed vascular pathology in diabetic pregnancy.
Xie
Lijuan
L
Perinatal Research Group, Kolling Institute of Medical Research at Royal North Shore Hospital, University of Sydney, NSW, Australia.
Galettis
Anoula
A
Morris
Jonathan
J
Jackson
Christopher
C
Twigg
Stephen M
SM
Gallery
Eileen D M
ED
D000906:Antibodies; D002448:Cell Adhesion / Q000502:physiology*; D017931:DNA Primers; D003656:Decidua / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D010920:Placenta / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics
D000906:Antibodies; D017931:DNA Primers; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1