CD36-positive stress reticulocytosis in sickle cell anemia.
Vasoocclusive episodes in sickle cell anemia may be initiated by adherence of erythrocytes to endothelium, one mechanism of which involves thrombospondin binding to CD36 on the red blood cell (RBC). We compared CD36 expression and its relationship to stress reticulocytosis in patients with sickle cell anemia and other chronic hemolytic disorders, including some after splenectomy. Adults with sickle cell anemia had significantly more CD36-positive cells (4.1% +/- 3.4%, mean +/- SD, n = 12) in unfractionated blood than did normal adults, who had almost none (0.13% +/- 0.15%, n = 8, p < 0.05). In density-fractionated blood, sickle samples contained significantly more CD36-positive cells (39.8% +/- 21.9%, n = 10) in the lowest density layers than did splenectomized high-reticulocyte controls (8.5% +/- 6.4%, n = 4, p < 0.05). "Stress" reticulocytes (identified by their unique morphology) were significantly more frequent in low-density layers from sickle blood (44.3% +/- 23.9%, n = 10) than from nonsplenectomized high-reticulocyte controls (10.5% +/- 14.8%, n = 5, p < 0.05). There was a strong correlation (r = 0.92) between stress reticulocyte count and number of CD36-positive cells for all patients except thalassemics, in whom CD36-positive cells were more frequent than stress reticulocytes. Flow cytometry confirmed that the maximal CD36 signal was found on immature reticulocytes. We conclude that CD36-positive stress reticulocytes occur more frequently in sickle cell anemia than in other chronic hemolytic states, even after surgical splenectomy, suggesting that this enhanced CD36-positive stress reticulocytosis does not simply reflect absent splenic function. These results explain why RBCs from high-reticulocyte control patients fail to show the significant CD36-dependent thrombospondin-mediated adhesion to endothelium that is exhibited by sickle red cells.
Browne
P V
PV
Division of Hematology, Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Hebbel
R P
RP
D000755:Anemia, Sickle Cell / Q000097:blood*; D018955:CD36 Antigens / Q000097:blood*; D002499:Centrifugation, Density Gradient; D005434:Flow Cytometry; D006402:Hematologic Diseases / Q000097:blood*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D017701:Reticulocyte Count; D012156:Reticulocytes / Q000737:chemistry* / Q000648:ultrastructure; D013156:Splenectomy
D018955:CD36 Antigens