Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow

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 cl ose spatial relationship between both cell types which supports the paracri ne effect of platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1. Moreover, adhesion molecules including pi integrin rece ptors and fucosylated structures were determined to play an important role in these complex interactions. However, up to now the influence of megakary ocyte expressed glycoproteins CD41a and CD42b in these processes was not in vestigated. 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 fibro blasts, 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 fib roblast growth was evaluated by comparative megakaryocyte-fibroblast co-cul tures and inhibition studies using specific monoclonal antibodies (mabs). F ibroblast monocultures served as controls. In these experiments, selectin-s pecific antibodies significantly reduced megakaryocyte attachment to fibrob last 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 a ttachment to bone marrow fibroblasts. In contrast, the megakaryocyte glycop roteins CD41a and CD42b exert their effect on the megakaryocyte dependent f ibroblast growth. Altogether, it is tempting to speculate that the various interactions of these mediators reflect certain steps in the complex pathom echanisms causing the evolution of (reactive) myelofibrosis in hematopoieti c neoplasias accompanied by megakaryocytic proliferation. (C) 2000 Elsevier Science Ltd. All rights reserved.