title: Selectins (CD62L, CD62P) and megakaryocytic glycoproteins (CD41a, CD42b) mediate megakaryocyte-fibroblast interactions in human bone marrow.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Cologne, Joseph-Stelzmann-Str. 9, D-50934, Cologne, Germany. c.wickenhauser@uni-koeln.de
authors.forename: C
authors.initials: C
authors.lastname: Wickenhauser
authors.forename: B
authors.initials: B
authors.lastname: Schmitz
authors.forename: S E
authors.initials: SE
authors.lastname: Baldus
authors.forename: F
authors.initials: F
authors.lastname: Henze
authors.forename: P
authors.initials: P
authors.lastname: Farahmand
authors.forename: S
authors.initials: S
authors.lastname: Frimpong
authors.forename: J
authors.initials: J
authors.lastname: Thiele
authors.forename: R
authors.initials: R
authors.lastname: Fischer
mesh_terms: D001853:Bone Marrow / Q000502:physiology*; D002448:Cell Adhesion; D018920:Coculture Techniques; D005347:Fibroblasts / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D019041:L-Selectin / Q000502:physiology*; D008533:Megakaryocytes / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000502:physiology*
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D019041:L-Selectin