The development of platelet factor 4 (PF4)/heparin (H) antibodies initiates the morbidity of heparin-induced thrombocytopenia (HIT). This application seeks to elucidate the cellular basis of the PF4/H immune resposne using an optimized murine immunization model developed in our laboratory. Studies with this model have shown that PF4/H ultra large complexes (ULCs) potently induce PF4/H antibody (Ab) formation, directly activate DCs and induce proliferation of antigen-naive T-cells. Based on these observations, we hypothesize that PF4/H ULCs are not processed and presented as conventional antigens, but activate the immune system as SAGS. To test this hypothesis, we propose the following

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL110860-01A1
Application #
8534257
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$339,811
Indirect Cost
$126,001
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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