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Evidence for integrin receptor involvement in megakaryocyte‐fibroblast interaction: A possible pathomechanism for the evolution of myelofibrosis
Author(s) -
Schmitz Beate,
Thiele Juergen,
Otto Frauke,
Farahmand Parvis,
Henze Franc,
Frimpong Semra,
Wickenhauser Claudia,
Fischer Robert
Publication year - 1998
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199809)176:3<445::aid-jcp1>3.0.co;2-o
Subject(s) - megakaryocyte , fibronectin , fibroblast , integrin , microbiology and biotechnology , receptor , biology , myelofibrosis , chemistry , immunology , cell culture , haematopoiesis , extracellular matrix , stem cell , biochemistry , genetics , bone marrow
Megakaryocytes are assumed to be functionally linked with the evolution of myelofibrosis, complicating chronic myeloproliferative disorders. It has already been shown that megakaryocytes will promote fibroblast growth in vitro when in spatial proximity. Here, we demonstrate that the integrin receptors α3β1 and α5β1 are involved in this megakaryocyte‐fibroblast interaction. Upon addition of anti‐α3 and ‐α5 antibodies to megakaryocyte‐fibroblast cocultures, fibroblast growth was significantly impaired, and megakaryocyte attachment to the fibroblast feederlayer was significantly reduced. Unilateral blocking of megakaryocytes with anti‐α3 or ‐α5 antibodies resulted in a suppression of adhesion, probably reflecting the prominent function of fibronectin receptors on the megakaryocyte surface. Moreover, the oligopeptide RGDS (Asp‐Gly‐Asp‐Ser) caused a significant reduction of fibroblast growth as well as megakaryocyte adhesion. This feature reinforces that fibronectin receptors are involved. In addition, fibroblast proliferation was impaired by the application of fibronectin antibodies recognizing the cell‐binding domain. However, no effect was observable with respect to megakaryocyte adhesion. In conclusion, our in vitro studies demonstrate the involvement of β1‐integrins, in particular the fibronectin receptor in the megakaryocyte‐dependent fibroblast proliferation and therefore suggest a pivotal role of megakaryocytes in the complex pathomechanism causing myelofibrosis. J. Cell. Physiol. 176:445–455, 1998. © 1998 Wiley‐Liss, Inc.