Wickenhauser C, Thiele J, Schmitz B, Frimpong S, Neumann I, Schramm K, Zankovich R, Fischer R
Institute of Pathology, University of Cologne, Germany.
Leuk Res. 1999 Mar;23(3):299-306. doi: 10.1016/s0145-2126(98)00142-8.
Lysozyme, a myelomonocytic marker not only exerts bacteriolytic, but also immunomodulatoric properties and was found to bind to the glycosaminoglycan serglycin, an important constituent of the extracellular matrix (ECM). Pathological serum lysozyme levels were described in chronic myeloproliferative disorders (CMPDs) and other hematological conditions. In this context it is remarkable that in polycythemia rubra vera (PV), characterized by a proliferation particularly of the megakaryo- and erythropoiesis, serum lysozyme levels behave independently of the numbers of myelomonocytic cells in peripheral blood. To elucidate whether megakaryopoiesis might be the source of the 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) polyglobuly (PG). In confirmation of previous results, quantification of serum lysozyme levels showed a slight elevation in the cohort of PV patients which was not correlated with the leukocyte count. Applying an immunohistochemical assay we were able to demonstrate intracytoplasmic lysozyme storage in megakaryocytes. Moreover, performing the reverse hemolytic plaque assay (RHPA), 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 megakaryocytes spontaneously secreted lysozyme. After rhIL-3 treatment the secretion of lysozyme remained unchanged in PV but increased to 14% in PG. These findings suggest that the extent of megakaryocytic lysozyme secretion might discriminate PV from reactive conditions. Although a direct involvement of lysozyme in the regulation of aberrant megakaryopoiesis in PV is not likely, the results of the present study point to the possibility that lysozyme could be involved in the interactions of PV megakaryocytes with ECM. Moreover, the response to rhIL-3 significantly discriminates PV megakaryocytes from megakaryocytes of the PG group.
溶菌酶是一种髓单核细胞标志物，不仅具有溶菌特性，还具有免疫调节特性，并且被发现可与细胞外基质（ECM）的重要成分糖胺聚糖丝甘蛋白聚糖结合。慢性骨髓增殖性疾病（CMPD）和其他血液学疾病中描述了病理性血清溶菌酶水平。在这种情况下，值得注意的是，在以巨核细胞和红细胞生成尤其增殖为特征的真性红细胞增多症（PV）中，血清溶菌酶水平的变化与外周血中髓单核细胞的数量无关。为了阐明巨核细胞生成是否可能是血清溶菌酶增加的来源，我们对来自PV患者骨髓的分离和富集的巨核细胞进行了一项实验研究。将结果与一组反应性（吸烟者）红细胞增多症（PG）患者进行了比较。证实先前的结果，血清溶菌酶水平的定量显示PV患者队列中有轻微升高，这与白细胞计数无关。应用免疫组织化学分析，我们能够证明巨核细胞内有溶菌酶储存。此外，进行反向溶血空斑试验（RHPA），这是一种能够在单细胞水平检测分泌蛋白的技术，我们发现54%的PV巨核细胞，但只有3%的PG巨核细胞自发分泌溶菌酶。rhIL-3治疗后，PV中溶菌酶的分泌保持不变，但PG中增加到14%。这些发现表明巨核细胞溶菌酶分泌的程度可能区分PV与反应性疾病。虽然溶菌酶不太可能直接参与PV中异常巨核细胞生成的调节，但本研究结果指出溶菌酶可能参与PV巨核细胞与ECM相互作用的可能性。此外，对rhIL-3的反应显著区分了PV巨核细胞与PG组的巨核细胞。
