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PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI.

Publication ,  Journal Article
Kasthuri, RS; Glover, SL; Jonas, W; McEachron, T; Pawlinski, R; Arepally, GM; Key, NS; Mackman, N
Published in: Blood
May 31, 2012

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 31, 2012

Volume

119

Issue

22

Start / End Page

5285 / 5293

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboplastin
  • Thrombocytopenia
  • Receptors, IgG
  • Platelet Factor 4
  • Monocytes
  • Male
  • MAP Kinase Signaling System
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Kasthuri, R. S., Glover, S. L., Jonas, W., McEachron, T., Pawlinski, R., Arepally, G. M., … Mackman, N. (2012). PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood, 119(22), 5285–5293. https://doi.org/10.1182/blood-2011-06-359430
Kasthuri, Raj S., Sam L. Glover, William Jonas, Troy McEachron, Rafal Pawlinski, Gowthami M. Arepally, Nigel S. Key, and Nigel Mackman. “PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI.Blood 119, no. 22 (May 31, 2012): 5285–93. https://doi.org/10.1182/blood-2011-06-359430.
Kasthuri RS, Glover SL, Jonas W, McEachron T, Pawlinski R, Arepally GM, et al. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood. 2012 May 31;119(22):5285–93.
Kasthuri, Raj S., et al. “PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI.Blood, vol. 119, no. 22, May 2012, pp. 5285–93. Pubmed, doi:10.1182/blood-2011-06-359430.
Kasthuri RS, Glover SL, Jonas W, McEachron T, Pawlinski R, Arepally GM, Key NS, Mackman N. PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood. 2012 May 31;119(22):5285–5293.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

May 31, 2012

Volume

119

Issue

22

Start / End Page

5285 / 5293

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboplastin
  • Thrombocytopenia
  • Receptors, IgG
  • Platelet Factor 4
  • Monocytes
  • Male
  • MAP Kinase Signaling System
  • Immunology
  • Humans