First Author | Wen L | Year | 2022 |
Journal | Cell Rep | Volume | 39 |
Issue | 9 | Pages | 110876 |
PubMed ID | 35649374 | Mgi Jnum | J:325332 |
Mgi Id | MGI:7284828 | Doi | 10.1016/j.celrep.2022.110876 |
Citation | Wen L, et al. (2022) A humanized beta2 integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo. Cell Rep 39(9):110876 |
abstractText | beta2 integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting beta2 integrin activation in mice hindered the study of beta2 integrin-related immune responses in vivo. Here, we generated a humanized beta2 integrin knockin mouse strain by targeting the human beta2 integrin coding sequence into the mouse Itgb2 locus to enable imaging of beta2 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 beta2 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 beta2 integrins are activated in association with elevated neutrophil adhesion in lung and liver. Thus, these mice enable studies of beta2 integrin activation in vivo. |