Platelet-erythrocyte adhesion in sickle cell disease.
BACKGROUND
The abnormal adherence of sickle red blood cells (sRBC) to other cell types likely contributes to vaso-occlusion. Increased numbers of platelet-erythrocyte aggregates (PEA) and platelet activation have been described in sickle cell disease. The present study was undertaken to determine the contribution, if any, of the extracellular matrix protein thrombospondin to the adhesion of sRBC and platelets.


METHODS
Platelet activation and PEA were measured using fluorescent-labeled monoclonal antibodies and flow cytometry. Platelet red-cell adhesion was measured by a gravity sedimentation assay. Erythrocyte-bound thrombospondin (TSP) was determined by enzyme-linked immunoabsorbant assay (ELISA).


RESULTS
Our studies demonstrate significant platelet activation and adhesion of sRBC to platelets in sickle cell disease. Thrombospondin was detected on sRBC. There was variable inhibition of sRBC-platelet adhesion by antibodies to CD36 (thrombospondin receptor) and antibodies to thrombospondin.


CONCLUSIONS
Thrombospondin on sRBC may mediate, at least in part, sRBC-platelet adhesion in sickle cell disease. The study of heterotypic cell-cell interactions is important in understanding the pathogenesis of vaso-occlusion in sickle cell disease.
Wun
T
T
Division of Hematology-Oncology, UC Davis, School of Medicine, Sacramento 95817, USA.
Paglieroni
T
T
Field
C L
CL
Welborn
J
J
Cheung
A
A
Walker
N J
NJ
Tablin
F
F
D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000502:physiology*; D018955:CD36 Antigens / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000502:physiology*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006112:Gravitation; D006450:Hemoglobin SC Disease / Q000503:physiopathology*; D006801:Humans; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000502:physiology; D019699:Thrombospondins / Q000032:analysis / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D019699:Thrombospondins