Endothelial TLR4 Expression Mediates Vaso-Occlusive Crisis in Sickle Cell Disease.

ABSTRACT: Heme, released from red blood cells in sickle cell disease (SCD), interacts with toll-like receptor 4 (TLR4) to activate NF-κB leading to the production of cytokines and adhesion molecules which promote inflammation, pain, and vaso-occlusion. In SCD, TLR4 inhibition has been shown to modulate heme-induced microvascular stasis and lung injury. We sought to delineate the role of endothelial verses hematopoietic TLR4 in SCD by developing a TLR4 null transgenic sickle mouse. We bred a global Tlr4^-/- deficiency state into Townes-AA mice expressing normal human adult hemoglobin A and Townes-SS mice expressing sickle hemoglobin S. SS-Tlr4^-/- had similar complete blood counts and serum chemistries as SS-Tlr4 ^+/+ mice. However, SS-Tlr4^-/

SUBMITTER: Beckman JD 

PROVIDER: S-EPMC7851052 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature