Impaired adhesion of neutrophils expressing Slc44a2/HNA-3b to VWF protects against NETosis under venous shear rates

Abstract Genome-wide association studies linked expression of the human neutrophil antigen 3b (HNA-3b) epitope on Slc44a2 protein with a 30% decreased risk venous thrombosis (VT) in humans. is ubiquitous transmembrane identified as receptor for von Willebrand factor (VWF). To explain link between and VT, we wanted to determine how expressing either HNA-3a or HNA-3b neutrophils could modulate their adhesion activation VWF under flow. Transfected HEK293T cells homozygous HNA-3a– HNA-3b–coding allele were purified from healthy donors perfused flow chambers coated at shear rates (100 s−1). was required Slc44a2-mediated 100 s−1. This occur independently β2 integrin enhanced when preactivated lipopolysaccharide. Moreover, specific conditions high concentration act “second hit,” inducing formation extracellular traps. Neutrophil mobilization also measured by intravital microscopy venules SLC44A2-knockout wild-type mice after histamine-induced endothelial degranulation. Mice lacking showed massive reduction recruitment inflamed mesenteric venules. Our results show that Slc44a2/HNA-3a important veins inflammation submitted shears. The fact Slc44a2/HNA-3b have different response tested thus reduced VT