The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice.

ABSTRACT: Vaso-occlusive crises, thrombosis, inflammation, and immune dysregulation contribute to organ damage and poor outcomes in sickle cell disease (SCD). Because neutrophils and dysregulated extracellular trap formation (NETosis) contribute to sickle pathophysiology, and the spleen tyrosine kinase (Syk) signaling pathway is a key driver of NETosis, we investigated the effect of targeting Syk with fostamatinib (R788). Specifically, we studied the effect of a selective Syk inhibitor, R788, on hematologic and biochemical parameters, NETosis, platelet P-selectin expression, and platelet-neutrophil aggregate formation in Townes sickle mice at baseline and after exposure to pathophysiological stressors (tumor necrosis factor α [TNF-α] and hypoxia-reoxygenation). Our results showed that at baseline R7

SUBMITTER: Parachalil Gopalan B 

PROVIDER: S-EPMC12768911 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature