Haematologica
HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
QUICK SEARCH:   [advanced]


     

Haematologica, Vol 92, Issue 8, 1091-1098 doi:10.3324/haematol.10702
Copyright © 2007 by Ferrata Storti Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Goldin-Lang, P.
Right arrow Articles by Rauch, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Goldin-Lang, P.
Right arrow Articles by Rauch, U.

Disorders of Hemostasis

Effect of ionizing radiation on cellular procoagulability and co-ordinated gene alterations

Petra Goldin-Lang, Klaus Pels, Quoc-Viet Tran, Bjoern Szotowski, Frank Wittchen, Silvio Antoniak, Tobias Willich, Henning Witt, Michael Hummel, Dido Lenze, Wolfgang Poller, Heinz-Peter Schultheiss, Ursula Rauch

From the Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany (PG-L, KP, Q-VT, BS, FW, SA, TW, WP, H-PS, UR); Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany (HW); Department of Pathology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany (MH, DL)

Correspondence: Ursula Rauch, MD, Medical Clinic II, Charité-Universitätsmedizin Berlin Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: ursula.rauch{at}charite.de

Background and Objectives: Ionizing radiation (IR) is associated with thrombotic vascular occlusion predicting a poor clinical outcome. Our study examined whether IR induced tissue factor (TF) expression and procoagulability. We further investigated coordinated gene alterations associated with TF upregulation in the myelomonocytic leukemia THP-1 cells.

Design and Methods: TF expression was determined by quantitative Reverse Transcriptase (TaqMan®) PCR, TF ELISA and TF activity by a two stage chromogenic assay in the time course of days 1, 3, 7, 10, and 17 post IR. To detect IR-induced alterations in gene expression, Affymetrix HG U133 Plus 2.0 microarrays were used.

Results: IR induced a significant increase in TF/GAPDH mRNA ratios and cellular TF protein on days 3 and 7 post IR (20 Gy [p≤0.01] and 40 Gy [p≤0.01 vs. control]), suggesting a late and persistent induction of TF. An increase in cellular TF activity was already found 1 day post IR (20 Gy and 40 Gy [p≥0.001] vs. control respectively), suggesting IR immediately alters the cellular thrombogenicity. TF upregulation post IR was confirmed in PBMNCs. Gene expression profiling showed IR increased the expression of inflammatory and apoptosis-related pathways known to be involved in the regulation of TF expression.

Interpretation and Conclusions: TF upregulation together with inflammation and apoptosis may increase the thrombogenicity of tissues. The demonstrated upregulation of TF might play a pivotal role in radiation associated thrombosis.

Key words: gene expression profiles, ionizing radiation, myelomonocytic cell line THP-1, procoagulability, tissue factor.






HOME HELP FEEDBACK TABLE OF CONTENTS ARCHIVE SUBSCRIPTIONS
Copyright © 2007 by the Ferrata Storti Foundation.