The kinetics of E-selectin- and P-selectin-induced intermediate activation of integrin αLβ2 on neutrophils

• DOI: 10.1242/jcs.258046
• Publication Date: 2021-08-26T09:24:48Z
• Authors: Fangyuan Zhou; Fang Zhang; Veronika I. Zarni...; Larissa Doudy; Zhou Yuan; Kaitao Li; Rodger P. McEver; Hang Lu; Cheng Zhu
• Keywords: Cooperativity; E-selectin; P-selectin

ABSTRACT Selectins and integrins are key players in the adhesion signaling cascade that recruits leukocytes to inflamed tissues. Selectin binding induces β2 integrin slow leukocyte rolling. Here, a micropipette was used characterize neutrophil E-selectin intercellular molecule-1 (ICAM-1) at room temperature. The time-dependent frequency displayed two-stage kinetics, with an E-selectin-mediated fast increase low plateau followed by high mediated intermediate-affinity of αLβ2 ICAM-1. activation required more than 5 s contact spleen tyrosine kinase (Syk) activity. A multi-zone channel analyze P-selectin separate zones receptors or antibodies, finding inverse relationship between rolling velocity on ICAM-1 dose, dose-dependent change from bent extended conformations closed headpiece faster 37°C Activation exhibited different levels cooperativity persistent times depending strength duration selectin stimulation. These results define precise timing kinetics intermediate E- P-selectins.