Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM.
Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin alpha(5) and to a lesser extent with anti-alpha(3) integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.
Wautier
Marie-Paule
MP
INSERM U665, Paris, France.
El Nemer
Wassim
W
Gane
Pierre
P
Rain
Jean-Didier
JD
Cartron
Jean-Pierre
JP
Colin
Yves
Y
Le Van Kim
Caroline
C
Wautier
Jean-Luc
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D008188:Lutheran Blood-Group System; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D011087:Polycythemia Vera / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013927:Thrombosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014471:Umbilical Veins / Q000378:metabolism / Q000473:pathology; D000097794:Kalinin
D000906:Antibodies; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D053614:Janus Kinase 2; D008188:Lutheran Blood-Group System; D009363:Neoplasm Proteins; D000097794:Kalinin; C090228:BCAM protein, human; C095100:ICAM4 protein, human; C507924:JAK2 protein, human