دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: A humanized β2 integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo.
المؤلفون: Wen, Lai, Marki, Alex, Wang, Zhihao, Orecchioni, Marco, Makings, Jeffrey, Billitti, Monica, Wang, Erpei, Suthahar, Sujit S.A., Kim, Kenneth, Kiosses, William B., Mikulski, Zbigniew, Ley, Klaus
المصدر: Cell Reports; May2022, Vol. 39 Issue 9, pN.PAG-N.PAG, 1p
مستخلص: β 2 integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting β 2 integrin activation in mice hindered the study of β 2 integrin-related immune responses in vivo. Here, we generated a humanized β 2 integrin knockin mouse strain by targeting the human β 2 integrin coding sequence into the mouse Itgb2 locus to enable imaging of β 2 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 2 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 2 integrins are activated in association with elevated neutrophil adhesion in lung and liver. Thus, these mice enable studies of β 2 integrin activation in vivo. [Display omitted] • Humanized β 2 integrin knockin mice show β 2 integrin activation in vivo • Activated β 2 integrins accumulate at the rear of neutrophils against blood flow • Activated β 2 integrins are concentrated at the uropod of neutrophils during TEM • β 2 integrins are activated in intravascular neutrophils of LPS-treated mice Wen et al. generated a reporter mouse for analysis of leukocyte β 2 integrin activation in vivo and show the dynamics and subcellular localization of β 2 integrin activation during neutrophil adhesion and transendothelial migration. This mouse also allows analysis of β 2 integrin activation in disease models. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:26391856
DOI:10.1016/j.celrep.2022.110876