Author
Buka, Richard JMontague, Samantha J
Moran, Luis A
Martin, Eleyna M
Slater, Alexandre
Watson, Steve P
Nicolson, Phillip L R
Publication date
2023-10-26Subject
Haematology
Metadata
Show full item recordAbstract
Platelet factor 4 (PF4) is an abundant chemokine that is released from platelet α-granules on activation. PF4 is central to the pathophysiology of vaccine-induced immune thrombocytopenia and thrombosis (VITT) in which antibodies to PF4 form immune complexes with PF4, which activate platelets and neutrophils through Fc receptors. In this study, we show that PF4 binds and activates the thrombopoietin receptor, cellular myeloproliferative leukemia protein (c-Mpl), on platelets. This leads to the activation of Janus kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription (STAT) 3 and STAT5, leading to platelet aggregation. Inhibition of the c-Mpl-JAK2 pathway inhibits platelet aggregation to PF4, VITT sera, and the combination of PF4 and IgG isolated from VITT patient plasma. The results support a model in which PF4-based immune complexes activate platelets through binding of the Fc domain to FcγRIIA and PF4 to c-Mpl.Citation
Buka RJ, Montague SJ, Moran LA, Martin EM, Slater A, Watson SP, Nicolson PLR. PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood. 2024 Jan 4;143(1):64-69. doi: 10.1182/blood.2023020872.Type
ArticlePMID
37883794Journal
BloodPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1182/blood.2023020872