A humanized β₂ integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation...

β₂ integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting β₂ integrin activation in mice hindered the study of β₂ integrin-related immune responses in vivo. Here, we generated a humanized β₂ integrin knockin mouse strain by targeting the human β₂ integrin coding sequence into the mouse Itgb2 locus to enable imaging of β₂ integrin activation using the KIM127 (extension) and mAb24 (high-affinity) reporter antibodies. Using a CXCL1-induced acute inflammation model, we show the local dynamics of β₂ integrin activation in arresting neutrophils in vivo in venules of the mouse cremaster muscle. Activated integrins are highly concentrated in a small area at the rear of arresting neutrophils in vivo. In a high-dose lipopolysaccharide model, we find that β₂ integrins are activated in association with elevated neutrophil adhesion in lung and liver. Thus, these mice enable studies of β₂ integrin activation in vivo.