A Common Genetic Variant in @entity11709 Enhances XXXX Neutrophil Priming and Impacts Length of Intensive Care Stay in Pediatric Sepsis.

@entity6415 @entity1 @entity295 @entity26165 @entity19892 @entity326 @entity26 @entity26087 @entity41642 @entity2938 @entity36459 @entity11709 @entity2939
UNASSIGNED: @entity6415 ( @entity6415 ) achieve an intermediate or primed state of activation following stimulation with certain agonists. Primed @entity6415 have enhanced responsiveness to subsequent stimuli, which can be beneficial in eliminating microbes but may cause host tissue damage in certain disease contexts, including @entity295 . As @entity6415 priming by @entity2939 agonists is well described, we hypothesized that ligation of @entity26087 or @entity2938 /6 would prime @entity6415 . Surprisingly, @entity6415 from only a subset of donors were primed in response to the @entity26087 agonist, Pam3CSK4, although @entity6415 from all donors were primed by the @entity26165 agonist, @entity36459 . Priming responses included generation of intracellular and extracellular reactive @entity26 species, MAPK phosphorylation, integrin activation, secondary granule exocytosis, and cytokine secretion. Genotyping studies revealed that @entity6415 responsiveness to Pam3CSK4 was enhanced by a common single-nucleotide polymorphism (SNP) in @entity11709 ( @entity41642 ). Notably, @entity6415 from donors with the SNP had higher surface levels of @entity11709 and were demonstrated to have enhanced association of @entity11709 with the endoplasmic reticulum chaperone @entity19892 . We analyzed @entity11709 genotypes in a pediatric @entity295 database and found that @entity1 with @entity295 or @entity326 who had a positive blood culture and were homozygous for the SNP associated with neutrophil priming had prolonged pediatric intensive care unit length of stay. We conclude that this @entity11709 SNP leads to excessive @entity6415 priming in response to cell stimulation. Based on our finding that septic @entity1 with this SNP had longer pediatric intensive care unit stays, we speculate that this SNP results in hyperinflammation in diseases such as @entity295 .
