A humanized β integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo.

β integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting β integrin activation in mice hindered the study of β integrin-related immune responses in vivo. Here, we generated a humanized β integrin knockin mouse strain by targeting the human β integrin coding sequence into the mouse Itgb2 locus to enable imaging of β 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 β 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 β integrins are activated in association with elevated neutrophil adhesion in lung and liver. Thus, these mice enable studies of β integrin activation in vivo.