TY - JOUR
T1 - Abnormal properties of red blood cells suggest a role in the pathophysiology of Gaucher disease
AU - Franco, Melanie
AU - Collec, Emmanuel
AU - Connes, Philippe
AU - van den Akker, Emile
AU - Billette de Villemeur, Thierry
AU - Belmatoug, Nadia
AU - von Lindern, Marieke
AU - Ameziane, Nejma
AU - Hermine, Olivier
AU - Colin, Yves
AU - Le van Kim, Caroline
AU - Mignot, Cyril
PY - 2013
Y1 - 2013
N2 - Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase deficiency. It is notably characterized by splenomegaly, complex skeletal involvement, ischemic events of the spleen and bones, and the accumulation of Gaucher cells in several organs. We hypothesized that red blood cells (RBCs) might be involved in some features of GD and studied the adhesive and hemorheologic properties of RBCs from GD patients. Hemorheologic analyses revealed enhanced blood viscosity, increased aggregation, and disaggregation threshold of GD RBCs compared with control (CTR) RBCs. GD RBCs also exhibited frequent morphologic abnormalities and lower deformability. Under physiologic flow conditions, GD RBCs adhered more strongly to human microvascular endothelial cells and to laminin than CTR. We showed that Lu/BCAM, the unique erythroid laminin receptor, is overexpressed and highly phosphorylated in GD RBCs, and may play a major role in the adhesion process. The demonstration that GD RBCs have abnormal rheologic and adhesion properties suggests that they may trigger ischemic events in GD, and possibly phagocytosis by macrophages, leading to the appearance of pathogenic Gaucher cells
AB - Gaucher disease (GD) is a lysosomal storage disorder caused by glucocerebrosidase deficiency. It is notably characterized by splenomegaly, complex skeletal involvement, ischemic events of the spleen and bones, and the accumulation of Gaucher cells in several organs. We hypothesized that red blood cells (RBCs) might be involved in some features of GD and studied the adhesive and hemorheologic properties of RBCs from GD patients. Hemorheologic analyses revealed enhanced blood viscosity, increased aggregation, and disaggregation threshold of GD RBCs compared with control (CTR) RBCs. GD RBCs also exhibited frequent morphologic abnormalities and lower deformability. Under physiologic flow conditions, GD RBCs adhered more strongly to human microvascular endothelial cells and to laminin than CTR. We showed that Lu/BCAM, the unique erythroid laminin receptor, is overexpressed and highly phosphorylated in GD RBCs, and may play a major role in the adhesion process. The demonstration that GD RBCs have abnormal rheologic and adhesion properties suggests that they may trigger ischemic events in GD, and possibly phagocytosis by macrophages, leading to the appearance of pathogenic Gaucher cells
U2 - https://doi.org/10.1182/blood-2012-07-442467
DO - https://doi.org/10.1182/blood-2012-07-442467
M3 - Article
C2 - 23212518
SN - 0006-4971
VL - 121
SP - 546
EP - 555
JO - Blood
JF - Blood
IS - 3
ER -