Polycythemia vera megakaryocytes store and release lysozyme to a higher extent than megakaryocytes in secondary polycythemia (polyglobuly)

Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also i mmunomodulatoric properties and was found to bind to the glycosaminoglycan serglycin, an important constituent of the extracellular matrix (ECM). Path ological serum lysozyme levels were described in chronic myeloproliferative disorders (CMPDs) and other hematological conditions. In this context it i s remarkable that in polycythemia rubra vera (PV), characterized by a proli feration particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave independently of the numbers of myelomonocytic cells in perip heral blood. To elucidate whether megakaryopoiesis might be the source of t he increased serum lysozyme, we performed an experimental study on isolated and enriched megakaryocytes derived from bone marrow of patients with PV. Findings were compared to a group of patients with reactive (smoker's) poly globuly (PG). In confirmation of previous results, quantification of serum lysozyme levels showed a slight elevation in the cohort of PV patients whic h was not correlated with the leukocyte count. Applying an immunohistochemi cal assay we were able to demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover, performing the reverse hemolytic plaque assay (RH PA), a technique which enables detection of secreted proteins at the single cell level, we found that 54% of the PV, but only 3% of the PG megakaryocy tes spontaneously secreted lysozyme. After rhIL-3 treatment the secretion o f lysozyme remained unchanged in PV but increased to 14% in PG. These findi ngs suggest that the extent of megakaryocytic lysozyme secretion might disc riminate PV from reactive conditions. Although a direct involvement of lyso zyme in the regulation of aberrant megakaryopoiesis in PV is not likely, th e results of the present study point to the possibility that lysozyme could be involved in the interactions of PV megakaryocytes with ECM. Moreover, t he response to rhIL-3 significantly discriminates PV megakaryocytes from me gakaryocytes of the PG group. (C) 1999 Elsevier Science Ltd. All rights res erved.