BACKGROUND: @entity281 lyses red blood cells, releasing haemoglobin (Hb) into the plasma. Although recent studies showed that immune cells recognize redox-active cytotoxic extracellular Hb (metHb) bound to pathogen-associated molecular patterns (PAMPs), currently available information is limited to experiments performed in defined conditions using single cell lines. Therefore, a systemic approach targeting primary whole blood cells is required to better understand the cellular immune defence against metHb and PAMPs, when under a @entity281 . METHODS: We investigated how @entity1 white blood cells, including neutrophils, respond to metHb and lipoteichoic acid (LTA) by measuring reactive @entity26 species (ROS), signalling mediators (ERK and @entity1435 ), NF-kB, cytokines, elastase secretion and cell activation markers. FINDINGS: metHb activates NF-kB in @entity2938 -expressing HEK293 cells but not in normal or @entity6801 -expressing HEK293 cells. Treatment of isolated neutrophils with metHb increased production of ROS and expressions of @entity687 , @entity310 , and @entity9536 , which were further enhanced by metHb  +  LTA complex. While LTA stimulated the survival of neutrophils, it caused apoptotic cell death when complexed with metHb. The activation of neutrophils by metHb  +  LTA was subdued by the presence of other types of white blood cells. INTERPRETATION: metHb and metHb  +  LTA complex are ligands of @entity2938 , inducing an unconventional TLR signalling pathway. Neutrophils are a highly sensitive cell type to metHb  +  LTA complex. During a @entity281 , white blood cells in the vicinity crosstalk to modulate neutrophil TLR-signalling induced by metHb and LTA.

Response of Neutrophils to Extracellular Haemoglobin and LTA in XXXX Blood System.

@entity1 :: ('9606', 'Species') :: ['human'] @entity310 :: ('7124', 'Gene') :: ['TNFa'] @entity9536 :: ('3684', 'Gene') :: ['CD11b'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity6801 :: ('54106', 'Gene') :: ['TLR9'] @entity2938 :: ('7097', 'Gene') :: ['TLR2'] @entity281 :: ('MESH:D007239', 'Disease') :: ['haemolytic infection', 'Haemolytic infection'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity687 :: ('3576', 'Gene') :: ['IL-8']
@entity1 :: (9606,Species) :: ['Human']
