BioSpace Collaborative

Academic/Biomedical Research
News & Jobs
Biotechnology and Pharmaceutical Channel Medical Device and Diagnostics Channel Clinical Research Channel BioSpace Collaborative    Job Seekers:  Register | Login          Employers:  Register | Login  

NEWSLETTERS
Free Newsletters
Archive
My Subscriptions

NEWS
News by Subject
News by Disease
News by Date
PLoS
Search News
Post Your News
JoVE

CAREER NETWORK
Job Seeker Login
Most Recent Jobs
Search Jobs
Post Resume
Career Fairs
Career Resources
For Employers

HOTBEDS
Regional News
US & Canada
  Biotech Bay
  Biotech Beach
  Genetown
  Pharm Country
  BioCapital
  BioMidwest
  Bio NC
  BioForest
  Southern Pharm
  BioCanada East
  C2C Services & Suppliers™
Europe
Asia

DIVERSITY

PROFILES
Company Profiles

INTELLIGENCE
Research Store

INDUSTRY EVENTS
Research Events
Post an Event
RESOURCES
Real Estate
Business Opportunities

PLoS By Category | Recent PLoS Articles
Biochemistry - Hematology - Immunology

Outside-In Signalling Generated by a Constitutively Activated Integrin aIIbß3 Impairs Proplatelet Formation in Human Megakaryocytes
Published: Monday, April 23, 2012
Author: Loredana Bury et al.

by Loredana Bury, Alessandro Malara, Paolo Gresele, Alessandra Balduini

Background

The interaction of megakaryocytes with matrix proteins of the osteoblastic and vascular niche is essential for megakaryocyte maturation and proplatelet formation. Fibrinogen is present in the vascular niche and the fibrinogen receptor aIIbß3 is abundantly expressed on megakaryocytes, however the role of the interaction between fibrinogen and aIIbß3 in proplatelet formation in humans is not yet fully understood. We have recently reported a novel congenital macrothrombocytopenia associated with a heterozygous mutation of the ß3 subunit of aIIbß3. The origin of thrombocytopenia in this condition remains unclear and this may represent an interesting natural model to get further insight into the role of the megakaryocyte fibrinogen receptor in megakaryopoiesis.

Methodology/Principal Findings

Patients' peripheral blood CD45+ cells in culture were differentiated into primary megakaryocytes and their maturation, spreading on different extracellular matrix proteins, and proplatelet formation were analyzed. Megakaryocyte maturation was normal but proplatelet formation was severely impaired, with tips decreased in number and larger in size than those of controls. Moreover, megakaryocyte spreading on fibrinogen was abnormal, with 50% of spread cells showing disordered actin distribution and more evident focal adhesion points than stress fibres. Integrin aIIbß3 expression was reduced but the receptor was constitutively activated and a sustained, and substrate-independent, activation of proteins of the outside-in signalling was observed. In addition, platelet maturation from preplatelets was impaired.

Conclusions/Significance

Our data show that constitutive activation of aIIbß3-mediated outside-in signalling in human megakaryocytes negatively influences proplatelet formation, leading to macrothombocytopenia.

  More...