Increased Adhesion of Red Blood Cells from Patients with Polycythemia Vera Is Mediated by Lu/B-CAM and Laminin alpha 5.

Polycythemia vera (PV) is associated to a high risk of vascular thrombosis which is related to red blood cell (RBC) volume and platelet activation. We have investigated whether, beside high hematocrit, RBCs exhibit qualitative abnormalities. Along this line we have measured RBC adhesion to human umbilical vein endothelial cell (HUVEC) under static and flow conditions. A group of 38 PV patients and one of 36 normal subjects were explored. Adhesion molecule expression using specific antibodies (anti-CD36, CD49d, ICAM-4, Lu/B-CAM, CD147, CD47) and flow cytometry were determined on RBCs. In addition antibodies directed against adhesion molecules or recombinant Lu/B-CAM or VCAM molecules were tested in the adhesion assays. PV-RBC adhesion was found to be increased 3.33 folds (2–4.5) compared to normal RBCs (p<0.001). The extent of adhesion was correlated to Lu/B-CAM expression on RBC (p<0.001) and was inhibited by polyclonal or monoclonal anti-Lu/B-CAM antibodies and soluble Lu/B-CAM recombinant molecules but not VCAM molecules. Adhesion of PV-RBCs activated HUVEC and stimulated VCAM expression, but stimulation of HUVEC by TNF did not increase PV-RBC adhesion. The increase of adhesion was apparently limited to a population of RBCs which are not reticulocytes and which cannot be detached from HUVEC even by a shear stress above 2 Pa. On HUVEC side the adhesion can be blocked by anti-laminin alpha 5 chain antibodies but not anti-Lu/B-CAM. These results indicate that Lu/B-CAM on PV-RBC is responsible for the increased adhesiveness to laminin expressed on HUVEC. This may be one of the factors involved in thrombotic events.