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

Abstract

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 invivo. 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 invivo in venules of the mouse cremaster muscle. Activated integrins are highly concentrated in a small area at the rear of arresting neutrophils invivo. 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 invivo.