Wickenhauser C, Schmitz B, Baldus S E, Henze F, Farahmand P, Frimpong S, Thiele J, Fischer R
Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50934, Cologne, Germany.
Leuk Res. 2000 Dec;24(12):1013-21. doi: 10.1016/s0145-2126(00)00063-1.
Previous in vitro studies are in keeping with the finding that isolated and enriched megakaryocytes attach to bone marrow fibroblasts and generate an increased growth of these cells. This process was assumed to depend on a close spatial relationship between both cell types which supports the paracrine effect of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1. Moreover, adhesion molecules including beta1 integrin receptors and fucosylated structures were determined to play an important role in these complex interactions. However, up to now the influence of megakaryocyte expressed glycoproteins CD41a and CD42b in these processes was not investigated. In addition, the role of megakaryocytic CD62P and also of CD62L, both adhesion molecules of the selectin group, could also be of interest. Following isolation and enrichment of bone marrow megakaryocytes and fibroblasts, both cell populations were characterized regarding their expression of these factors by applying immunocytochemical techniques. Additionally, their influence on adhesion of megakaryocytes to fibroblasts as well as fibroblast growth was evaluated by comparative megakaryocyte-fibroblast co-cultures and inhibition studies using specific monoclonal antibodies (mabs). Fibroblast monocultures served as controls. In these experiments, selectin-specific antibodies significantly reduced megakaryocyte attachment to fibroblast feeder layers and fibroblast growth in the co-cultures. The effect of CD41a and CD42b specific antibodies was limited to megakaryocyte-dependent fibroblast growth. These results elucidate the involvement of the selectins CD62P and CD62L in the basal activation of megakaryocytes inducing their attachment to bone marrow fibroblasts. In contrast, the megakaryocyte glycoproteins CD41a and CD42b exert their effect on the megakaryocyte dependent fibroblast growth. Altogether, it is tempting to speculate that the various interactions of these mediators reflect certain steps in the complex pathomechanisms causing the evolution of (reactive) myelofibrosis in hematopoietic neoplasias accompanied by megakaryocytic proliferation.
分离并富集的巨核细胞可附着于骨髓成纤维细胞，并使这些细胞的生长增加。这一过程被认为依赖于两种细胞类型之间紧密的空间关系，这种关系支持血小板衍生生长因子（PDGF）和转化生长因子（TGF）-β1的旁分泌作用。此外，包括β1整合素受体和岩藻糖基化结构在内的黏附分子在这些复杂的相互作用中起重要作用。然而，迄今为止，尚未研究巨核细胞表达的糖蛋白CD41a和CD42b在这些过程中的影响。此外，选择素家族的黏附分子巨核细胞CD62P以及CD62L的作用也可能值得关注。在分离并富集骨髓巨核细胞和成纤维细胞后，通过应用免疫细胞化学技术对这两种细胞群体的这些因子表达进行了表征。此外，通过比较巨核细胞-成纤维细胞共培养以及使用特异性单克隆抗体（mab）的抑制研究，评估了它们对巨核细胞与成纤维细胞黏附以及成纤维细胞生长的影响。成纤维细胞单培养用作对照。在这些实验中，选择素特异性抗体显著降低了巨核细胞与成纤维细胞饲养层的黏附以及共培养中成纤维细胞的生长。CD41a和CD42b特异性抗体的作用仅限于巨核细胞依赖性成纤维细胞生长。这些结果阐明了选择素CD62P和CD62L参与巨核细胞的基础激活，诱导其附着于骨髓成纤维细胞。相比之下，巨核细胞糖蛋白CD41a和CD42b对巨核细胞依赖性成纤维细胞生长发挥作用。总的来说，很容易推测这些介质的各种相互作用反映了导致造血肿瘤伴巨核细胞增殖（反应性）骨髓纤维化演变的复杂病理机制中的某些步骤。
