Enhanced adherence of human uremic erythrocytes to vascular endothelium: role of phosphatidylserine exposure.
BACKGROUND
The exposure of phosphatidylserine (PS) on the outer leaflet of erythrocyte membrane may have several pathophysiological consequences including increased erythrocyte adherence to endothelial cells, a finding that seems relevant in pathologies with reported vascular injury.


METHODS
Because PS externalization increases in erythrocytes from patients suffering from chronic uremia, which is frequently associated with vascular damage, the adherence of uremic erythrocytes to human umbilical vein endothelial cell (HUVEC) monolayers and the role of PS exposure on such cell-cell interaction were studied.


RESULTS
The number of uremic erythrocytes adhering to HUVEC was markedly greater than with normal erythrocytes and significantly correlated (r = 0.88) with the percentage of PS-exposing erythrocytes in the population. Adhesion to the monolayers was significantly decreased when uremic erythrocytes were preincubated with either annexin V or PS-containing liposomes, and was strongly greater for PS-positive than PS-negative fluorescence-activated cell sorter (FACS)-sorted uremic erythrocytes. Binding occurred preferentially in the gaps of HUVEC monolayers and was enhanced by matrix exposure. Uremic erythrocytes adhered to immobilized thrombospondin, and binding to endothelial cells was significantly reduced when monolayers were incubated with antibodies to thrombospondin.


CONCLUSIONS
These findings suggest that PS externalization may promote increased uremic erythrocyte adhesion to endothelium, possibly via a direct interaction with matrix thrombospondin.
Bonomini
Mario
M
Institute of Nephrology, Department of Medicine, G. d'Annunzio University, SS Annunziata Hospital, Via dei Vestini, 66100 Chieti, Italy. m.bonomini@nephro.unich.it
Sirolli
Vittorio
V
Gizzi
Federico
F
Di Stante
Silvio
S
Grilli
Alfredo
A
Felaco
Mario
M
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010718:Phosphatidylserines / Q000494:pharmacology*; D019699:Thrombospondins / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology; D014511:Uremia / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010718:Phosphatidylserines; D019699:Thrombospondins